Gene Report

Basic Information

Approved Symbol	CREB1
Approved Name	cAMP responsive element binding protein 1
Location	2q34
Position	chr2:208394616-208470284 (+)
External Links	Entrez Gene: 1385 Ensembl: ENSG00000118260 UCSC: uc002vcc.3 HGNC ID: 2345
No. of Studies (Positive/Negative)	12(10/2)
Type	Literature-origin; Protein mapped

Positive relationships between CREB1 and MDD (count: 7)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
CREB1	Liu, 2010	patients and normal controls	P-value=0.00003241	There was strong positive association between the rs10932201...... There was strong positive association between the rs10932201-rs6740584 haplotype of the CREB1 and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022) More...
cAMP-responsive element-binding protein (CREB)	Zubenko, 2002	patients and normal controls		The region between the markers that yielded the peak LOD sco...... The region between the markers that yielded the peak LOD score includes the CREB1 gene More...
CREB1	Zubenko, 2003	patients and normal controls	P-value << 0.0001	The highest maximum LOD score observed, 8.19 (genome-wide a...... The highest maximum LOD score observed, 8.19 (genome-wide adjusted P << 0.0001), occurred for Recurrent Major Depressive Disorder (R-MDD) at D2S2321 (205 cM), located 121 kb proximal to CREB1 More...
CREB1	Maher, 2010	patients and normal controls		The results continue to support sex-specific linkage of the ...... The results continue to support sex-specific linkage of the CREB1 region to mood disorders among women from families with RE-MDD. More...
CREB1	Zubenko, 2003	patients and normal controls		Sequence variations in the CREB1 promoter and intron 8 have ...... Sequence variations in the CREB1 promoter and intron 8 have been detected that cosegregate with Mood Disorders, or their absence, in women from these families, identifying CREB1 as a sex-limited susceptibility gene for unipolar Mood Disorders. More...
CREB	Iga, 2007	patients and normal controls		Levels of HDAC5 and CREB mRNA were significantly higher in d...... Levels of HDAC5 and CREB mRNA were significantly higher in drug-free depressive patients than those of controls More...
CREB1	Belzeaux, 2010	patients and normal controls		We also observed that variations in other mRNA expression we...... We also observed that variations in other mRNA expression were associated with treatment efficacy or clinical improvement (CREB1, HDAC5, HSPA2, HTR1B, HTR2A, and SLC6A4/5HTT). More...

Positive relationships between CREB1 and other components at different levels (count: 3)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
CREB1		Steroids(steroids)	molecule	Zubenko, 2009	cell model		The results support the hypothesis that the A(-656) allele c...... The results support the hypothesis that the A(-656) allele contributes to the development of MDD in women through selective alteration of CREB1 promoter activity by female gonadal steroids in noradrenergic neuronal cells. More...
CREB		Emotion(anger expression)	cognition and behavior	Perlis, 2007	patients only	P-value=0.003	For the sample as a whole, one of six SNPs tested in this ge...... For the sample as a whole, one of six SNPs tested in this gene was significantly associated with anger expression (empirical p = .003). More...
CREB1		Emotion(responding to angry)	cognition and behavior	Perlis, 2008	normal people		The CREB1-linked single-nucleotide polymorphism was associat...... The CREB1-linked single-nucleotide polymorphism was associated with significant differential activation in an extended neural network responding to angry and other facial expressions. More...

Positive relationship network of CREB1 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between CREB1 and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
CREB1	Hettema JM, 2009	Patients and nomal controls		None of these markers were significant in stage 2 in either ...... None of these markers were significant in stage 2 in either sex individually or combined More...
CREB1	Crisafulli C, 2012	patients and normal controls		Participants were genotyped for 14 SNPs within CREB1, CREBBP...... Participants were genotyped for 14 SNPs within CREB1, CREBBP and CREM. We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. More...

Negative relationships between CREB1 and other components at different levels (count: 0)

CREB1 related SNPs in MK4MDD (count: 0)

CREB1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Cyclic AMP-responsive element-binding protein 1	P16220	7(7/0)	Literature-origin

CREB1 related GO terms (count: 47)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0007268	synaptic transmission	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0048011	nerve growth factor receptor signaling pathway	biological process	TAS
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity	molecular function	IDA[19861239]
GO:0042493	response to drug	biological process	IEA
GO:0034134	toll-like receptor 2 signaling pathway	biological process	TAS
GO:0045600	positive regulation of fat cell differentiation	biological process	ISS
GO:0001102	RNA polymerase II activating transcription factor binding	molecular function	IPI[19861239]
GO:0046889	positive regulation of lipid biosynthetic process	biological process	ISS
GO:0035666	TRIF-dependent toll-like receptor signaling pathway	biological process	TAS
GO:0007411	axon guidance	biological process	TAS
GO:0005634	nucleus	cellular component	IDA
GO:0001190	RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription	molecular function	IDA[19861239]
GO:0002224	toll-like receptor signaling pathway	biological process	TAS
GO:0050821	protein stabilization	biological process	ISS
GO:0005654	nucleoplasm	cellular component	TAS
GO:0003712	transcription cofactor activity	molecular function	TAS[8552098]
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IDA[19861239]
GO:0008063	Toll signaling pathway	biological process	TAS
GO:0034130	toll-like receptor 1 signaling pathway	biological process	TAS
GO:0002756	MyD88-independent toll-like receptor signaling pathway	biological process	TAS
GO:0008543	fibroblast growth factor receptor signaling pathway	biological process	TAS
GO:0034138	toll-like receptor 3 signaling pathway	biological process	TAS
GO:0040018	positive regulation of multicellular organism growth	biological process	IEA
GO:0007165	signal transduction	biological process	TAS
GO:0002755	MyD88-dependent toll-like receptor signaling pathway	biological process	TAS
GO:0010033	response to organic substance	biological process	IDA[8798441]
GO:0034142	toll-like receptor 4 signaling pathway	biological process	TAS
GO:0045087	innate immune response	biological process	TAS
GO:0045893	positive regulation of transcription, DNA-dependent	biological process	ISS
GO:0007595	lactation	biological process	IEA
GO:0048015	phosphatidylinositol-mediated signaling	biological process	TAS
GO:0005667	transcription factor complex	cellular component	IEA
GO:0019048	virus-host interaction	biological process	IEA
GO:0006468	protein phosphorylation	biological process	IDA[8798441]
GO:0046887	positive regulation of hormone secretion	biological process	IEA
GO:0008361	regulation of cell size	biological process	IEA
GO:0010944	negative regulation of transcription by competitive promoter binding	biological process	IDA[19861239]
GO:0035497	cAMP response element binding	molecular function	IDA[19861239]
GO:0000980	RNA polymerase II distal enhancer sequence-specific DNA binding	molecular function	IDA[19861239]
GO:0003700	sequence-specific DNA binding transcription factor activity	molecular function	IDA[8798441]
GO:0051403	stress-activated MAPK cascade	biological process	TAS
GO:0005515	protein binding	molecular function	IPI
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	TAS
GO:0007202	activation of phospholipase C activity	biological process	TAS
GO:0005730	nucleolus	cellular component	IDA
GO:0021983	pituitary gland development	biological process	IEA
GO:0005719	nuclear euchromatin	cellular component	IDA[19861239]

CREB1 related KEGG pathways (count: 5)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04612	antigen processing_and_presentation	Antigen processing and presentation
hsa04962	vasopressin regulated_water_reabsorption	Vasopressin-regulated water reabsorption	In the kidney, the antidiuretic hormone vasopressin (AVP) is...... In the kidney, the antidiuretic hormone vasopressin (AVP) is a critical regulator of water homeostasis by controlling the water movement from lumen to the interstitium for water reabsorption and adjusting the urinary water excretion. In normal physiology, AVP is secreted into the circulation by the posterior pituitary gland, in response to an increase in serum osmolality or a decrease in effective circulating volume. When reaching the kidney, AVP binds to V2 receptors on the basolateral surface of the collecting duct epithelium, triggering a G-protein-linked signaling cascade, which leads to water channel aquaporin-2 (AQP2) vesicle insertion into the apical plasma membrane. This results in higher water permeability in the collecting duct and, driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels, which are constitutively expressed on the basolateral side of these cells. When isotonicity is restored, reduced blood AVP levels results in AQP2 internalization, leaving the apical membrane watertight again. More...
hsa04916	melanogenesis	Melanogenesis	Cutaneous melanin pigment plays a critical role in camouflag...... Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism. More...
hsa05215	prostate cancer	Prostate cancer	The identification of key molecular alterations in prostate-...... The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes that catalyze conjunction of glutathione with harmful, electrophilic molecules, thereby protecting cells from carcinogenic factors. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by such carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. After therapeutic reduction in the levels of testosterone and dihydrotestosterone, the emergence of androgen-independent prostate cancer has been associated with mutations in the androgen receptor (AR) that permit receptor activation by other ligands, increased expression of androgen receptors accompanying AR amplification, and ligand-independent androgen-receptor activation. More...
hsa05016	huntingtons disease	Huntington's disease	Huntington disease (HD) is an autosomal-dominant neurodegene...... Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2+ signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NR2B/NR1 NMDAR activity, and destabilizing mitochondrial Ca2+ handling. As a result, stimulation of glutamate receptors leads to supranormal Ca2+ responses in HD MSN and mitochondrial Ca2+ overload. The mHtt translocates to the nucleus, where it forms intranuclear inclusions, though they are not primarily responsible for toxicity. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction. More...

CREB1 related BioCarta pathways (count: 11)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
MAPK_PATHWAY	mapk pathway	MAPKinase Signaling Pathway	The ever evolving mitogen-activated protein kinase (MAP kina...... The ever evolving mitogen-activated protein kinase (MAP kinase) pathways consist of four major groupings and numerous related proteins which constitute interrelated signal transduction cascades activated by stimuli such as growth factors, stress, cytokines and inflammation. The four major groupings are the Erk (red), JNK or SAPK (blue), p38 (green) and the Big MAPK or ERK5 (light blue) cascades. Signals from cell surface receptors such as GPCRs and growth factor receptors are transduced, directly or via small G proteins such as ras and rac, to multiple tiers of protein kinases that amplify these signals and/or regulate each other. The diagram is organized to illustrate the cascades by the background colors and also the tiers of kinases as indicated down the left hand side and separated by the horizontal dashed lines. In some cascades the first activation tier involves the MAPKKKKs, MAP kinase kinase kinase kinases or MAP4K proteins. The next tier are the serine/threonine MAPKKKs, MAP kinase kinase kinase or MAP3Ks such as RAF, TAK, ASK, and MEKK1. This level has the greatest amount of cross-communication curently known. The serine/threonine/tyrosine MAPKKs, MAP Kinase kinases or MAP2Ks, such as the MKK and MEK kinases, are one step up from the MAP kinase cascade, phosphorylating and activating these kinases. The focal tier, the MAPKs or MAP kinases includes JNK1, p38, and ERKs, and are the kinases that give each cascade its name BR>The endpoints of these cascades, shown in the bottom tier, includes the MAPK activated protein kinases (MAPKAPK) and some of the numerous transcription factors that regulate genes involved in apoptosis, inflammation, cell growth and differentiation NOTES:- The shared color and the bold arrows show the major flow of each cascade. - The smaller arrows indicate cross communication between cascades. In many cases this is restricted to certain cell types or requires additional factors. - Kinases that have been identified as MAP kinases based on sequence or structural homolgies but have not yet been assigned to a cascade have been placed out side the grouping backrgounds. - The PAKs (p21 associated kinases) are not MAPKs but participate in the transduction to the JNK cascade are included for this reason.) - MEK4 appears to function in both the JNK and p38 cascades and so has a mixed color. MEK4 signal is much stronger in the JNK than the p38 cascade and so the bold arrow towards the JNK and the dashed arrow towards the p38 cascade indicate the relative strengths of signaling. - For space and readability concerns not all interactions and stimuli are indicated and the scaffold and phosphatase proteins are not shown. More...
HIF_PATHWAY	hif pathway	Hypoxia-Inducible Factor in the Cardiovascular System	Hypoxia (or low O2 levels) affects various pathologies. Firs...... Hypoxia (or low O2 levels) affects various pathologies. First, tissue ischemia, a variation in O2 tension caused by hypoxia/reoxygenation, can lead to endothelial cell changes. For example, long periods of ischemia result in endothelial changes, such as vascular leakage, resulting in varicose veins. In more severe situations, ischemia can lead to myocardial or cerebral infarction and retinal vessel occlusion. Of interest, HIF-1 is stabilized prior to induction of vascular endothelial growth factor (VEGF) expression during acute ischemia in the human heart. Second, pulmonary hypertension associated with chronic respiratory disorders results from persistent vasoconstriction and vascular remodeling. Third, hypoxic gradients created in enlarging solid tumors trigger expression of genes containing hypoxia response element (HRE)s such as those involved in angiogenesis. This allows subsequent delivery of O2, nutrients, and further tumor growth. Vascular remodeling is an important component to tumorigenesis; without proper blood supply, delivery of oxygen may occur by diffusion, but becomes inefficient in tumors greater than 1 mm in diameter. Short-term hypoxia can also elevate platelet numbers, while prolonged exposure may cause some degree of thrombocytopenia in response to increased levels of erythropoetin (EPO). Another disorder involving inadequate responses to hypoxia is preeclampsia, a pathology of pregnancy thought to be caused by improper differentiation of placental trophoblast cells due to poorly controlled O2 tension or improper hypoxia-inducible factor (HIF)-mediated responses. The primary molecular mechanism of gene activation during hypoxia is through HIF-1. Several genes involved in cellular differentiation are directly or indirectly regulated by hypoxia. These include EPO, LDH-A, ET-1, transferrin, transferrin receptor, VEGF, Flk-1, Flt-1, platelet-derived growth factor- (PDGF-), basic fibroblast growth factor (bFGF), and others genes affecting glycolysis. HIF-1 is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors known to induce gene expression by binding to a ~50-bp HRE containing a core 5'-ACGTG-3' sequence. bHLH-PAS proteins heterodimerize to form transcription complexes that regulate O2 homeostasis, circadian rhythms, neurogenesis, and toxin metabolism. Three bHLH-PAS proteins in vertebrates respond to hypoxia: HIF-1 , EPAS (HIF-2 ), and HIF-3. These dimerize with ARNT (aryl hydrocarbon receptor nuclear translocator protein), ARNT-2, or ARNT-3. HIF-1 is ubiquitinated and subsequently degraded in less than 5 minutes under normoxic conditions. Although several candidate O2-sensing molecules have emerged in the literature, the molecular basis of how cells sense O2 levels is poorly characterized. pVHL, the protein product of a tumor-suppressor gene responsible for von Hippel Lindau disease, is implicated in this O2-sensing system by its association with HIF-1 , targeting it for ubiquitin-mediated degradation. Similarly, F-box-containing proteins recognize substrates of the ubiquitin ligases, targeting them for phosphorylation-dependent ubiquitination and proteosomal degradation. In addition to F-boxes, most of these proteins also contain a WD40 or a leucine-rich repeat (LLR) domain that presumably functions as a Ser/Thr binding module. A second family of proteins assisting the ubiquitin ligases share a region designated SOCS-box (originally from the suppressor of cytokine signaling proteins SOCS). Under low O2 (<5% O2) HIF-1 is stabilized leading to the formation of a functional transcription factor complex with ARNT. This complex is the master regulator of O2 homeostasis and induces a network of genes involved in angiogenesis, erythropoiesis, and glucose metabolism. More...
HCMV_PATHWAY	hcmv pathway	Human Cytomegalovirus and Map Kinase Pathways	To replicate in the host cell, viruses commandeer cellular s...... To replicate in the host cell, viruses commandeer cellular signaling pathways. Cytomegalovirus (CMV) is a DNA virus with that is widespread in the population but usually causes disease only in immunocompromised individuals and is also a viral cause of birth defects. One of the actions of CMV in the host cell is to stimulate MAP kinase pathways. Both p38 and ERK kinases are activated by CMV infection through activation map kinase kinases and inhibition of phosphatases. One result of Map kinase activation by CMV is activation of transcription of viral genes, increasing the production of viral gene products. Both p38 and ERK kinases contribute to the activation of viral genes by cellular transcription factors acting through the viral UL4 promoter at upstream and basal transcription elements. Another target of prolonged p38 activation during infection is Rb, contributing to viral replication. Activation of MKK1 and MKK2 leads to Erk1 and Erk2 activation, and phosphorylation of downstream targets. The MEKK1 kinase regulates the immediate early promoter indirectly through downstream kinase signaling and perhaps more directly through activation of NF-kB. Map kinase pathways activated by CMV converge on increased transcription of viral genes and increased replication of the viral genome. Better understanding of the mechanisms involved in the interaction of CMV with cellular signaling machinery will provide improved ways to treat CMV-mediated disease. More...
DREAM_PATHWAY	dream pathway	Repression of Pain Sensation by the Transcriptional Regulator DREAM	The molecular events that lead to the perception of pain are...... The molecular events that lead to the perception of pain are a key research field in medicine and drug discovery. The opioid receptors modulate pain signaling in response to endogenous peptide ligands and opiate drugs such as morphine. The kappa opioid receptor plays a key role in the profound analgesia of opiates and is activated by the endogenous peptide ligand dynorphin, encoded by the prodynorphin gene. Production of prodynorphin is transcriptionally regulated by a downstream regulatory element (DRE) in the prodynorphin gene. A transcription factor called DREAM (DRE antagonistic modulator) binds to the DRE and represses prodynorphin transcription when bound. DREAM binds calcium with 4 EF-hand motifs and the binding of DREAM to DNA is repressed in the presence of calcium. Many transcription factors are regulated by calcium indirectly through calcium sensitive kinases and phosphatases, but DREAM is unique to date in being a transcription factor that directly binds calcium and is regulated by calcium binding. DREAM may also regulate other genes such as c-fos. DREAM is expressed in spinal cord neurons in regions involved in pain signaling. The regulation of prodynorphin expression by DREAM also leads to the hypothesis that DREAM is involved in pain signaling. Transgenic mice lacking the DREAM gene were unusually pain insensitive and had elevated spinal levels of dynorphin and tonic activation of the kappa opioid receptor, supporting this hypothesis. Other functions of DREAM may exist such as regulation of presenilins and potassium channel activity in the heart. DREAM is also known as calsenilin and KChIP3 through its association with these other proteins. These processes were not affected in mice lacking the DREAM gene however. More...
ERK5_PATHWAY	erk5 pathway	Role of Erk5 in Neuronal Survival	Axons extend significant distances to innervate target tissu...... Axons extend significant distances to innervate target tissues. At the site of innervation, target tissues release neurotrophins including NGF, BDNF and neurotrophin-3 that stimulate the survival of the associated neuron. Local signaling by activated Trk receptors at the synaptic terminus mediates some presynaptic neuronal responses to neurotrophins. Map kinase pathways activated by Trk receptor activate Erk1 and Erk2 at the terminus stimulating axonal growth, and PI3K activates AKT in the terminus as well. Activation of these kinases does not propagate a signal to the cell body though and does not induce a transcriptional response. This local signaling at the terminus or local signaling at the cell body appears distinct from the signaling pathway that transduces the survival signal from the target tissue. Retrograde axonal transport plays an essential role in neuronal survival induced by neurotrophins released at the target tissue. Failure of retrograde neurotrophin signaling may play a role in neurodegenerative conditions. The neuronal survival signal is initiated by binding of neurotrophins to Trk receptors in the presynaptic membrane, then travels back along the axon to the neuronal cell body. To transmit the signal back along the axon, activated Trk receptors are internalized through receptor-mediated endocytosis and receptor containing vesicles then rapidly travel back to the cell body along axonal microtubules. Several reports indicate that neurotrophins remain receptor-bound during the retrograde axonal transport to the cell body, but recently it was reported that retrograde transport of NGF was not required to induce neuronal survival. Once in the cell body, Trk receptors activate multiple pathways. A key pathway activated by Trk after retrograde transport involves Erk5, also called BMK1. Trk activates Mek5, which activates Erk5, inducing phosphorylation of the CREB and Mef2 transcription factors. Erk5 does not directly phosphorylate CREB, but translocates into the nucleus and phosphorylates the kinase Rsk, which phosphorylates CREB in turn. Both CREB and Mef2 induce a transcriptional program that contributes to neuronal survival. Local activation of Erk5 on the cell body does not appear to induce the same signaling system or neuronal survival, indicating that the retrograde transport is an essential part of the survival signaling system. Also, activation of Erk1 and Erk2 in the cell body can induce CREB activation and neuronal survival, but these kinases are not activated by neurotrophins applied to the axonal terminus. Another pathway activated by retrograde neurotrophin signaling though Erk5 is PI3 Kinase. More...
P38MAPK_PATHWAY	p38mapk pathway	p38 MAPK Signaling Pathway	p38 MAPKs are members of the MAPK family that are activated ...... p38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases of the Rho family (Rac, Rho, Cdc42). As with other MAPK cascades, the membrane-proximal component is a MAPKKK, typically a MEKK or a mixed lineage kinase (MLK). The MAPKKK phosphorylates and activated MKK3/5, the p38 MAPK kinase. MKK3/6 can also be activated directly by ASK1, which is stimulated by apoptotic stimuli. P38 MAK is involved in regulation of Hsp27 and MAPKAP-2 and several transcription factors including ATF2, STAT1, THE Max/Myc complex, MEF-2, ELK-1 and indirectly CREB via activation of MSK1. More...
CREB_PATHWAY	creb pathway	Transcription factor CREB and its extracellular signals	The transcription factor CREB binds the cyclic AMP response ...... The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity. Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133. Phosphorylation occurs at Ser133 via p44/42 MAP Kinase and p90RSK and also via p38 MAP Kinase and MSK1. CREB exhibit deficiencies in spatial learning tasks, while flies overexpressing or lacking CREB show enhanced or diminished learning, respectively. More...
CARM1_PATHWAY	carm1 pathway	Transcription Regulation by Methyltransferase of CARM1	Several forms of post-translational modification regulate pr...... Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known. More...
CACAM_PATHWAY	cacam pathway	Ca++/ Calmodulin-dependent Protein Kinase Activation	The calcium/calmodulin-dependent kinases (CaMKs) are involve...... The calcium/calmodulin-dependent kinases (CaMKs) are involved in a large number of cellular responses induced by hormones, neurotransmitters and other signalling. Elevation of calcium functions as a major second messenger, where the intracellular concentration of calcium can be maintained at extremely low levels and susequently increased following specific calcium-mobilizing stimuli. There are many buffers to the calcium fluxuations including membrane pumps and calcium-binding proteins that create discrete spatial control of its effectors and their targets. The current family of multifunctional calcium/calmodulin (CaM)-dependent protein kinases (CaMKs) consists of CaMKI, CaMKII and CaMKIV. These kinases translate and co-ordinate the calcium fluxuations into the appropriate cellular responses via phosphorylation. These kinases are partially regulated by the intracellular calcium receptor calmodulin (CaM), have common as well as unique features in their structure, regulation and activation. CaMKII, CaMKI and CaMKIV, have an autoregulatory domain that restricts or inhibits enzymic activity in the absence of calcium/CaM. Calcium/CaM binding alone produces maximal activity of CaMKII, whereas CaMKI and CaMKIV have an activation loop that requires phosphorylation of a threonine residue by CaMK kinase (CaMKK) for maximal activity. Two genes (alpha and beta) for CaMKK, which is also regulated by CaM, have been identified. The highest expression of these isoforms occurs in the brain but the activity of the CaMKs has been identified in most cell types. CaMKIV has a post-calmodulin autophosphorylation step that is not observed in CaMKI. The CaMKII multimer can autophosphorylate either the autoregulatory domain or the CaM-binding domain, producing diverse effects in its regulation and sensitivity to Calcium/CaM. Autophosphorylation of CaMKII can produce Calcium/CaM- independent activity (autonomous activity), without affecting its maximal Calcium/CaM-stimulated activity. The CaMKII autophosphorylation involves a kinase cascade of sorts, with each subunit of the multimeric enzyme acting as both kinase and kinase kinase. Autophosphorylation establishes a 1000-fold increase in the affinity for its activator Calcium/CaM (also known as CaM trapping); however, autophosphorylation within the CaM-binding domain following CaM dissociation of activated/autophosphorylated enzyme restricts or prevents CaM from rebinding (CaM capping). The mechanisms and consequences of autophosphorylation are central to the CaMKII enzyme's complex regulatory behavior enabling it to become differentially activated at different frequencies and levels of calcium spikes. The target proteins for the CaMKs are very similar. An example target of the CaMKs is the transcriptional activating protein CREB. The phosphorylation states of CREB after CaMK phosphorlyation differ by the additional phosphorylation of CREB at serine 142 that functions as an additional inhibitory site. This difference appears to be the result of adjacent amino acids. More...
GPCR_PATHWAY	gpcr pathway	Signaling Pathway from G-Protein Families	G-aS-coupled receptors stimulate adenylyl cyclase (AC), whic...... G-aS-coupled receptors stimulate adenylyl cyclase (AC), which synthesizes cAMP from ATP. In contrast Gai-coupled receptors inhibit AC and so reduce cAMP formation. The bg subunits from Gai and other G proteins are able to activate the MAP kinase pathways and PLCb. GPCRs coupled to the Gaq family of G proteins stimulate PLCb, which cleaves membrane phospholipids to produce IP3, which mobilizes intracellular calcium, and DAG, which activates PKC. Second messenger pathways then activate a range of effector systems to change cell behaviour; in many cases this includes the regulation of gene transcription. Dotted line shows a more indirect pathway. More...
ARENRF2_PATHWAY	arenrf2 pathway	Oxidative Stress Induced Gene Expression Via Nrf2	Reactive oxygen species (ROS) can damage biological macromol...... Reactive oxygen species (ROS) can damage biological macromolecules and are detrimental to cellular health. Electrophilic compounds, xenobiotics and antioxidants are sources of reactive oxygen species, creating oxidative stress that can harm cells. Enzymes are involved in the Phase II detoxification of xenobiotics to reduce cellular stress include glutathione transferases, quinone reductase, epoxide hydrolase, heme oxygenase, UDP-glucuronosyl transferases, and gamma-glutamylcysteine synthetase. Expression of these genes protects cells from oxidative damage and can prevent mutagenesis and cancer. Transcription of these enzymes is coordinately regulated through antioxidant response elements (AREs). Nrf2 (NF-E2-related factor 2) and Nrf1 are transcription factors that bind to AREs and activate these genes. Inactive Nrf2 is retained in the cytosol by association a complex with the cytoskeletal protein Keap1. Cytosolic Nrf2 is phosphorylated and translocates into the nucleus in response to protein kinase C activation and Map kinase pathways. In the nucleus, Nrf2 activate genes through AREs by interacting with transcription factors in the bZIP family, including CREB, ATF4 and fos or jun. Nrf2 activation of genes is opposed by small maf proteins, including MafG and MafK, maintaining a counterbalance to Nrf2 and balancing the oxidation level of the intracellular environment. More...

CREB1 related Reactome pathways (count: 23)

ID	Name	Description
Gene mapped Reactome pathways
REACT_20568	creb phophorylation_through_the_activation_of_ras	Ca2+ influx through the NMDA receptor initiates subsequent m...... Ca2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca2+ within the spine leads to phosphorylation of Cyclic AMP Response Element binding protein (CREB) at serine 133 which is involved in the transcription of genes that results in long lasting changes in the synapse. The phosphorylation of CREB by increased Ca2+ can be brought about by distinct molecular pathways that may involve MAP kinase, activation of adenylate cyclase, activation of CaMKII and/or the activation of CaMKIV. More...
REACT_21308	map kinases_activation_in_tlr_cascade	Mitogen activated protein kinase. There are three major grou...... Mitogen activated protein kinase. There are three major groups of MAP kinases the extracellular signal-regulated protein kinases ERK1/2. the p38 MAP kinase. the c-Jun NH-terminal kinases JNK. ERK1 and ERK2 are activated in response to growth stimuli. Both JNKs and p38-MAPK are activated in response to a variety of cellular and environmental stresses. The MAP kinases are activated by dual phosphorylation of Thr and Tyr within the tripeptide motif Thr-Xaa-Tyr. The sequence of this tripeptide motif is different in each group of MAP kinases: ERK (Thr-Glu-Tyr); p38 (Thr-Gly-Tyr); and JNK (Thr-Pro-Tyr). MAPK activation is mediated by signal transduction in the conserved three-tiered kinase cascade: MAPKKKK (MAP4K or MKKKK or MAPKKK Kinase) activates the MAPKKK. The MAPKKKs then phosphorylates a dual-specificity protein kinase MAPKK, which in turn phosphorylates the MAPK. The dual specificity MAP kinase kinases (MAPKK or MKK) differ for each group of MAPK. The ERK MAP kinases are activated by the MKK1 and MKK2; the p38 MAP kinases are activated by MKK3, MKK4, and MKK6; and the JNK pathway is activated by MKK4 and MKK7. The ability of MAP kinase kinases (MKKs, or MEKs) to recognize their cognate MAPKs is facilitated by a short docking motif (the D-site) in the MKK N-terminus, which binds to a complementary region on the MAPK. MAPKs then recognize many of their targets using the same strategy, because many MAPK substrates also contain D-sites. The upstream signaling events in the TLR cascade that initiate and mediate the ERK signaling pathway remain unclear. More...
REACT_15426	plc beta_mediated_events	The phospholipase C (PLC) family of enzymes is both diverse ...... The phospholipase C (PLC) family of enzymes is both diverse and complex. The isoforms beta, gamma and delta (each have subtypes) make up the members of this family. PLC hydrolyzes phosphatidylinositol bisphosphate (PIP2) into two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores while DAG activates protein kinase C isoforms which are involved in regulatory functions. More...
REACT_15370	neuroransmitter receptor_binding_and_downstream_transmission_in_the_postsynaptic_cell	The neurotransmitter in the synaptic cleft released by the p...... The neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein coupled receptors that function to transmit the signals from the post-synaptic membrane to the cell body. More...
REACT_12433	nuclear events_kinase_and_transcription_factor_activation	An important function of the kinase cascade triggered by neu...... An important function of the kinase cascade triggered by neurotrophins is to induce the phosphorylation and activation of transcription factors in the nucleus to initiate new programs of gene expression. Transcription factors directly activated by neurotrophin signalling are responsible for induction of immediate-early genes, many of which are transcription factors. These in turn are involved in the induction of delayed-early genes. More...
REACT_12056	trka signalling_from_the_plasma_membrane	Trk receptors signal from the plasma membrane and from intra...... Trk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes is slower but long lasting. Signalling from the plasma membrane is annotated here. TRK signalling leads to proliferation in some cell types and neuronal differentiation in others. Proliferation is the likely outcome of short term signalling, as observed following stimulation of EGFR (EGF receptor). Long term signalling via TRK receptors, instead, was clearly shown to be required for neuronal differentiation in response to neurotrophins. More...
REACT_12079	plc gamma1_signalling	The activation of phosphlipase C-gamma (PLC-gamma) and subse...... The activation of phosphlipase C-gamma (PLC-gamma) and subsequent mobilization of calcium from intracellular stores are essential for neurotrophin secretion. PLC-gamma is activated through the phosphorylation by TrkA receptor kinase and this form hydrolyses PIP2 to generate inositol tris-phosphate (IP3) and diacylglycerol (DAG). IP3 promotes the release of Ca2+ from internal stores and this results in activation of enzymes such as protein kinase C and Ca2+ calmodulin-regulated protein kinases. More...
REACT_13477	transmission across_chemical_synapses	Chemical synapses are specialized junctions that are used fo...... Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell. More...
REACT_6900	signaling in_immune_system	Humans are exposed to millions of potential pathogens daily,...... Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system. More...
REACT_20642	creb phosphorylation_through_the_activation_of_camkii	Ca2+ signal generated through NMDA receptor in the post-syna...... Ca2+ signal generated through NMDA receptor in the post-synaptic neuron activates adenylate cyclase signal transduction, leading to the activation of PKA and phosphorylation and activation of CREB-induced transcription. The isoforms of adenylate cyclase that are activated by Ca2+ in the brain are I, III and IX. More...
REACT_20593	post nmda_receptor_activation_events	Ca2+ influx through the NMDA receptor initiates subsequent m...... Ca2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca2+ within the spine leads to phosphorylation of Cyclic AMP Response Element binding protein (CREB) at serine 133 which is involved in the transcription of genes that results in long lasting changes in the synapse. The phosphorylation of CREB by increased Ca2+ can be brought about by distinct molecular pathways that may involve MAP kinase, activation of adenylate cyclase, activation of CaMKII and/or the activation of CaMKIV. More...
REACT_20563	activation of_nmda_receptor_upon_glutamate_binding_and_postsynaptic_events	NMDA receptors are a subtype of ionotropic glutamate recepto...... NMDA receptors are a subtype of ionotropic glutamate receptors that are specifically activated by a glutamate agonist N-methyl-D-aspartate (NMDA). Activation of NMDA receptor involves opening of the ion channel that allows the influx of Ca2+. NMDA receptors are central to activity dependent changes in synaptic strength and are predominantly involved in the synaptic plasticity that pertain to learning and memory. A unique feature of NMDA receptor unlike other glutamate receptors is the requirement of dual activation of the NMDA receptor, which require both voltage dependent and ligand dependent activation. At resting membrane potential the NMDA receptors are blocked by Mg2+. The voltage dependent Mg2+ block is relieved upon depolarization of the post-synpatic membrane. The ligand dependent activation of the NMDA receptor requires co-activation by two ligands, namely glutamate and glycine. NMDA receptors are coincidence detector, and are activated only if there is simultaneous activation of both pre and post-synaptic cell. Upon activation NMDA receptors allow the influx of Ca2+ that initiates various molecular signaling cascades that are involved in the process of learning and memory. More...
REACT_9053	cam pathway	Calmodulin (CaM) is a small acidic protein that contains fou...... Calmodulin (CaM) is a small acidic protein that contains four EF-hand motifs, each of which can bind a calcium ion, therefore it can bind up to four calcium ions. The protein has two approximately symmetrical domains, separated by a flexible hinge region. Calmodulin is the prototypical example of the EF-hand family of Ca2+-sensing proteins. Changes in intracellular Ca2+ concentration regulate calmodulin in three distinct ways. First, by directing its subcellular distribution. Second, by promoting association with different target proteins. Third, by directing a variety of conformational states in calmodulin that result in target-specific activation. Calmodulin binds and activates several effector protein (e.g. the CaM-dependent adenylyl cyclases, phosphodiesterases, protein kinases and the protein phosphatase calcineurin). More...
REACT_6782	traf6 mediated_induction_of_the_antiviral_cytokine_ifn_alpha_beta_cascade	In human, together with ubiquitin-conjugating E2-type enzyme...... In human, together with ubiquitin-conjugating E2-type enzymes UBC13 and UEV1A and IKK(NEMO), leading to the activation of the kinases. Xia et all., 2009 demonstrated in vitro that unlike polyubiquitin chains covalently attached to TRAF6 or IRAK, TAB2 and NEMO-associated ubiquitin chains were found to be unanchored and susceptible to N-terminal ubiquitin cleavage. Only K63-linked polyubiquitin chains, but not monomeric ubiquitin, activated TAK1 in a dose-dependent manner.Optimal activation of the IKK complex was achieved using ubiquitin polymers containing both K48 and K63 linkages. Furthermore, the authors proposed that the TAK1 complexes might be brougt in close proximity by binding several TAB2/3 to a single polyubiquitin chain to facilitate TAK1 kinases trans-phosphorylation. Alternativly, the possibility that polyUb binding promotes allosteric activation of TAK1 complex should be considered. More...
REACT_15295	opioid signalling	Opioids are chemical substances similar to opiates, the acti...... Opioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as the enkephalins, the endorphins or the dynorphins. Opioids possess powerful analgesic and sedative effects, and are widely used as pain-killers. Their main side-effect is the rapid establishment of a strong addiction. Opioids receptors are G-protein coupled receptors (GPCR). There are four classes of receptors: mu (MOR), kappa (KOR) and delta (DOR), and the nociceptin receptor (NOP). More...
REACT_12464	pi3k akt_signalling	PI3K/AKT signalling is a major regulator of neuron survival....... PI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell death and survival. In addition, it may also use metabolic pathways to regulate cell survival.The PI3K/AKT pathway also affects axon diameter and branching and regulates small G proteins like RhoA , which control the behaviour of the F-actin cytoskeleton. Moreover, through its connection with the TOR pathway, it promotes translation of a subset of mRNAs. More...
REACT_11061	signalling by_ngf	Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles i...... Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in minute amounts, by a variety of tissues. They signal through two types of receptors: TRK tyrosine kinase receptors (TRKA, TRKB, TRKC), which specifically interact with the different neurotrophins, and p75NTR, which interacts with all neurotrophins. TRK receptors are reported in a variety of tissues in addition to neurons. p75NTRs are also widespread. Neurotrophins and their receptors are synthesized as several different splice variants, which differ in terms of their biological activities. The nerve growth factor (NGF) was the first growth factor to be identified and has served as a model for studying the mechanisms of action of neurotrophins and growth factors. The mechanisms by which NGF generates diverse cellular responses have been studied extensively in the rat pheochromocytoma cell line PC12. When exposed to NGF, PC12 cells exit the cell cycle and differentiate into sympathetic neuron-like cells. Current data show that signalling by the other neurotrophins is similar to NGF signalling. More...
REACT_6966	toll receptor_cascades	In human, ten members of the Toll-like receptor (TLR) family...... In human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) domain in their cytoplasmic region and an Ig-like domain in the extracellular region, where each is enriched with a varying number of leucine-rich repeats (LRRs). Each TLR can recognize specific microbial pathogen components. The binding pathogens component of the TLRs initializes signaling pathways that lead to induction of Interferon alpha/beta. There are three main signaling pathways: the first is a MyD88-dependent pathway that is common to all TLRs, except TLR3; the second is a TRAM-dependent pathway that is peculiar to TLR3 and TLR4 and is mediated by TRIF and RIP1; and the third is a TRAF6-mediated pathway peculiar to TLR3. More...
REACT_18334	ncam signaling_for_neurite_out_growth	The neural cell adhesion molecule, NCAM, is a member of the ...... The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. The role of NCAM in neural differentiation and synaptic plasticity is presumed to depend on the modulation of intracellular signal transduction cascades. NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons. NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements. More...
REACT_18266	axon guidance	Axon guidance / axon pathfinding is the process by which neu...... Axon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, which senses the guidance cues in the environment through guidance cue receptors and responds by undergoing cytoskeletal changes that determine the direction of axon growth. Guidance cues present in the surrounding environment provide the necessary directional information for the trip. These extrinsic cues have been divided into attractive or repulsive signals that tell the growth cone where and where not to grow. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules and their receptors that guide axons. These include netrins, Slits, semaphorins, and ephrins, and their cognate receptors, DCC and or uncoordinated-5 (UNC5), roundabouts (Robo), neuropilin and Eph. In addition, many other classes of adhesion molecules are also used by growth cones to navigate properly which include NCAM and L1CAM. More...
REACT_21328	mapk targets_nuclear_events_mediated_by_map_kinases	MAPKs are protein kinases that, once activated, phosphorylat...... MAPKs are protein kinases that, once activated, phosphorylate their specific cytosolic or nuclear substrates at serine and/or threonine residues. Such phosphorylation events can either positively or negatively regulate substrate, and thus entire signaling cascade activity. The major cytosolic target of activated ERKs are RSKs. Other ERK nuclear targets include c-Myc, HSF1 (Heat-Shock Factor-1), STAT1/3 (Signal Transducer and Activator of Transcription-1/3), and many more transcription factors. Activated p38 MAPK is able to phosphorylate a variety of substrates, including transcription factors STAT1, p53, ATF2 (Activating transcription factor 2), MEF2 (Myocyte enhancer factor-2), protein kinases MSK1, MNK, MAPKAPK2/3, death/survival molecules (Bcl2, caspases), and cell cycle control factors (cyclin D1). JNK, once activated, phosphorylates a range of nuclear substrates, including transcription factors Jun, ATF, Elk1, p53, STAT1/3 and many other factors. JNK has also been shown to directly phosphorylate many nuclear hormone receptors. For example, peroxisome proliferator-activated receptor 1 (PPAR-1) and retinoic acid receptors RXR and RAR are substrates for JNK. Other JNK targets are heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Other adaptor and scaffold proteins have also been characterized as nonnuclear substrates of JNK. More...
REACT_6802	innate immunity_signaling	Innate immunity encompases the nonspecific part of immunity ...... Innate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup More...
REACT_6783	toll like_receptor_3_cascade	Toll-like receptor 3 (TLR3) as was shown for mammals is expr...... Toll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and inflammatory responses of the innate immunity in combating viral infections. Mammalian TLR3 recognizes dsRNA, and that triggers the receptor to induce the activation of NF-kappaB and the production of type I interferons (IFNs). dsRNA-stimulated phosphorylation of two specific TLR3 tyrosine residues (Tyr759 and Tyr858) is essential for initiating TLR3 signaling pathways. More...

CREB1 related interactors from protein-protein interaction data in HPRD (count: 38)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
CREB1	VIM	Yes	yeast 2-hybrid	16169070
CREB1	SOX9	No	in vivo	19113914
CREB1	CEBPB	No	in vitro;in vivo;yeast 2-hybrid	12773552
CREB1	TSSK4	No	in vitro;yeast 2-hybrid	15964553
CREB1	THRA	Yes	in vitro;in vivo	12805224
CREB1	CHD3	No	yeast 2-hybrid	16169070
CREB1	MAPK14	No	in vivo	11377386
CREB1	SMARCA4	No	in vivo	16675956
CREB1	KCNIP3	No	in vitro;in vivo	12198160
CREB1	FHL5	No	in vivo;yeast 2-hybrid	11046156
CREB1	DYRK1A	No	in vivo	15694837
CREB1	ATF1	No	in vitro;in vivo	8384217 , 1655749
CREB1	KAT5	Yes	in vitro;in vivo	10720489
CREB1	PRKG1	No	in vitro	9687510 , 11175347 , 9829964 , 8688081
CREB1	RPS6KA5	No	in vitro;in vivo	9687510 , 11018520 , 11909979 , 16223362
CREB1	GTF2F2	No	in vivo	8628277
CREB1	RAB1A	Yes	yeast 2-hybrid	16169070
CREB1	GLI2	No	in vitro;in vivo	10074179
CREB1	RECQL5	No	yeast 2-hybrid	16169070
CREB1	RPS6KA3	No	in vitro;in vivo	9687510 , 11175347 , 9829964 , 8688081 , 11160957
CREB1	RPS6KA1	No	in vitro	9687510 , 11175347 , 9829964 , 8688081 , 12235136
CREB1	MAPKAPK2	No	in vitro	8887554
CREB1	AKT1	No	in vitro	9829964
CREB1	NR3C1	Yes	in vitro	7621901 , 8449898
CREB1	RPS6KA2	No	in vitro;in vivo	9687510 , 11175347 , 9829964 , 8688081 , 11698596
CREB1	ATM	Yes	in vitro	16293623 , 15073328
CREB1	CREBBP	Yes	in vitro;in vivo	9413984 , 15073328
CREB1	EDF1	No	in vitro	10567391
CREB1	C14orf1	No	yeast 2-hybrid	16169070
CREB1	SGK1	No	in vitro;in vivo	15733869
CREB1	SMARCA5	No	in vivo	16675956
CREB1	RPS6KA4	No	in vitro	9792677 , 9687510 , 11175347 , 9829964 , 8688081
CREB1	HPS6	No	yeast 2-hybrid	16169070
CREB1	CREM	Yes	in vitro;in vivo	7809053
CREB1	ABL1	No	in vivo	7565761
CREB1	SRF	No	in vitro;in vivo	9388250 , 7551568
CREB1	PDX1	No	in vivo	7505393
CREB1	GSK3B	Yes	in vivo	12162494

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways