Gene Report

Basic Information

Approved Symbol	GSK3B
Approved Name	glycogen synthase kinase 3 beta
Location	3q13.3
Position	chr3:119540800-119813264 (-)
External Links	Entrez Gene: 2932 Ensembl: ENSG00000082701 UCSC: uc003edm.3 HGNC ID: 4617
No. of Studies (Positive/Negative)	7(6/1)
Type	Literature-origin; SNP mapped; Protein mapped

Positive relationships between GSK3B and MDD (count: 5)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
GSK3beta	Inkster, 2010	patients and normal controls		We observed associations for polymorphisms in 5/10 GSK3beta ...... We observed associations for polymorphisms in 5/10 GSK3beta substrate genes More...
GSK3B	Zhang, 2010	patients and normal controls	P-value<0.05	Further gene-gene interaction analyses showed a significant ...... Further gene-gene interaction analyses showed a significant effect of a two-locus BDNF/GSK3B interaction with MDD (GSK3B rs6782799 and BDNF rs7124442) (corrected P = 0.011), and also for a three-locus interaction (GSK3B rs6782799, BDNF rs6265 and BDNF rs7124442) (corrected P = 0.019). More...
GSK3B	Saus, 2010	patients and normal controls		We identified a haplotype containing three SNPs (rs334555, r...... We identified a haplotype containing three SNPs (rs334555, rs119258668 and rs11927974) associated with age at onset (AAO) of the disorder (permutated P = 0.0025). More...
GSK3B	Yang, 2010	patients and normal controls	P-value=0.07	We observed a potential association between the GSK3B rs6782...... We observed a potential association between the GSK3B rs6782799 and MDD (P=0.07) More...
GSK-3beta	Oh, 2010	patients and normal controls	P-value<0.05	The level of GSK-3beta mRNA expression in the hippocampus wa...... The level of GSK-3beta mRNA expression in the hippocampus was significantly increased in the MDD group (n=8) compared with the control group (n=12, p<0.05). More...

Positive relationships between GSK3B 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
glycogen synthase kinase-3beta (GSK3beta)		Hippocampus(hippocampus)	brain morphology and function	Inkster, 2009	patients and normal controls	P-value=0.02	Rs6438552 in this gene showed 3 significant GM clusters in t...... Rs6438552 in this gene showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). More...
glycogen synthase kinase-3beta (GSK3beta)		Superior temporal gyrus(superior temporal gyri)	brain morphology and function	Inkster, 2009	patients and normal controls	P-value<0.05	Rs6438552 in this gene showed 3 significant GM clusters in t...... Rs6438552 in this gene showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). More...
GSK3B		Life events(negative life events)	environment	Yang, 2010	patients and normal controls		We observed a significant three-way interaction among BDNF r...... We observed a significant three-way interaction among BDNF rs6265, GSK3B rs6782799, and negative life events (corrected P-value, 0.011-0.012; cross-validation consistency, 7; prediction error, 0.4349). More...

Positive relationship network of GSK3B 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 GSK3B and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
GSK-3beta	Yoon HK, 2010	Patients and nomal controls		The results showed that the alleles, genotypes, and haploty...... The results showed that the alleles, genotypes, and haplotypes of the two SNPs do not differ between suicidal MDD subjects, non-suicidal MDD subjects, and normal controls. There was no difference in the haplotype frequency combination between the three groups. More...

Negative relationships between GSK3B and other components at different levels (count: 0)

GSK3B related SNPs in MK4MDD (count: 2)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs6438552	chr3:119631814(Forward)	intron_variant	1(1/0)
rs6782799	chr3:119610793(Forward)	intron_variant	1(1/0)

GSK3B related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Glycogen synthase kinase-3 beta	P49841	2(2/0)	Literature-origin

GSK3B related GO terms (count: 81)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0016301	kinase activity	molecular function	IDA[15448698]; TAS
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0006468	protein phosphorylation	biological process	IDA[11035810]
GO:0030010	establishment of cell polarity	biological process	IEA
GO:0045892	negative regulation of transcription, DNA-dependent	biological process	IEA
GO:0035372	protein localization to microtubule	biological process	IEA
GO:0001837	epithelial to mesenchymal transition	biological process	IMP[15448698]
GO:0045121	membrane raft	cellular component	IEA
GO:0045444	fat cell differentiation	biological process	IEA
GO:0010226	response to lithium ion	biological process	IEA
GO:0043066	negative regulation of apoptotic process	biological process	IDA[14744935]
GO:0090090	negative regulation of canonical Wnt receptor signaling pathway	biological process	TAS[19366350]
GO:0045719	negative regulation of glycogen biosynthetic process	biological process	TAS[19366350]
GO:0035556	intracellular signal transduction	biological process	IDA[14749367]
GO:0006611	protein export from nucleus	biological process	IEA
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	TAS
GO:0046827	positive regulation of protein export from nucleus	biological process	IDA[14744935]
GO:0005829	cytosol	cellular component	TAS
GO:0043197	dendritic spine	cellular component	IEA
GO:0043198	dendritic shaft	cellular component	IEA
GO:0043025	neuronal cell body	cellular component	IEA
GO:0008013	beta-catenin binding	molecular function	IPI[8638126]
GO:0001954	positive regulation of cell-matrix adhesion	biological process	IMP[18156211]
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IEA
GO:0005524	ATP binding	molecular function	IEA
GO:0048011	nerve growth factor receptor signaling pathway	biological process	TAS
GO:0044027	hypermethylation of CpG island	biological process	IEA
GO:0005977	glycogen metabolic process	biological process	IDA[8638126]
GO:0060070	canonical Wnt receptor signaling pathway	biological process	IC[9601641]; IDA[18787224]
GO:0001085	RNA polymerase II transcription factor binding	molecular function	IPI
GO:0031334	positive regulation of protein complex assembly	biological process	IDA[8638126]
GO:0050774	negative regulation of dendrite morphogenesis	biological process	IEA
GO:0030426	growth cone	cellular component	IEA
GO:0048168	regulation of neuronal synaptic plasticity	biological process	IEA
GO:0005813	centrosome	cellular component	IDA
GO:0005178	integrin binding	molecular function	IEA
GO:0021766	hippocampus development	biological process	IMP[19581563]
GO:0000320	re-entry into mitotic cell cycle	biological process	IEA
GO:0044337	canonical Wnt receptor signaling pathway involved in positive regulation of apoptotic process	biological process	IEA
GO:0032855	positive regulation of Rac GTPase activity	biological process	IMP[18156211]
GO:0071109	superior temporal gyrus development	biological process	IMP[19581563]
GO:0030529	ribonucleoprotein complex	cellular component	IEA
GO:0010800	positive regulation of peptidyl-threonine phosphorylation	biological process	IEA
GO:0032092	positive regulation of protein binding	biological process	ISS
GO:0006983	ER overload response	biological process	IDA[14744935]
GO:0005515	protein binding	molecular function	IPI[16365045]
GO:0035255	ionotropic glutamate receptor binding	molecular function	IEA
GO:0005730	nucleolus	cellular component	IDA
GO:0031333	negative regulation of protein complex assembly	biological process	IMP[16188939]
GO:0043407	negative regulation of MAP kinase activity	biological process	IEA
GO:0006349	regulation of gene expression by genetic imprinting	biological process	IEA
GO:0031625	ubiquitin protein ligase binding	molecular function	IPI
GO:2000738	positive regulation of stem cell differentiation	biological process	IEA
GO:0009887	organ morphogenesis	biological process	IEA
GO:2000466	negative regulation of glycogen (starch) synthase activity	biological process	TAS[19366350]
GO:0051534	negative regulation of NFAT protein import into nucleus	biological process	IMP[9072970]
GO:0007520	myoblast fusion	biological process	IEA
GO:0048015	phosphatidylinositol-mediated signaling	biological process	TAS
GO:0033138	positive regulation of peptidyl-serine phosphorylation	biological process	IEA
GO:0005737	cytoplasm	cellular component	IDA[19038973]
GO:0048471	perinuclear region of cytoplasm	cellular component	IEA
GO:0018105	peptidyl-serine phosphorylation	biological process	IDA[8638126]
GO:0005886	plasma membrane	cellular component	IDA
GO:0004674	protein serine/threonine kinase activity	molecular function	IDA[11035810]; ISS
GO:0045732	positive regulation of protein catabolic process	biological process	IC[16188939]
GO:0051059	NF-kappaB binding	molecular function	IPI[15465828]
GO:0050321	tau-protein kinase activity	molecular function	IDA[16365045]
GO:0034236	protein kinase A catalytic subunit binding	molecular function	IPI[11035810]
GO:0007411	axon guidance	biological process	TAS
GO:0016477	cell migration	biological process	IEA
GO:0005634	nucleus	cellular component	IDA
GO:2000077	negative regulation of type B pancreatic cell development	biological process	TAS[19366350]
GO:0042493	response to drug	biological process	IEA
GO:0032091	negative regulation of protein binding	biological process	IDA[16890161]
GO:0030877	beta-catenin destruction complex	cellular component	IDA[16188939]; TAS[19366350]
GO:0008543	fibroblast growth factor receptor signaling pathway	biological process	TAS
GO:0002039	p53 binding	molecular function	IDA[14744935]
GO:0019901	protein kinase binding	molecular function	IPI[18348280]
GO:0048156	tau protein binding	molecular function	IEA
GO:0032886	regulation of microtubule-based process	biological process	IMP

GSK3B related KEGG pathways (count: 18)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04510	focal adhesion	Focal adhesion	Cell-matrix adhesions play essential roles in important biol...... Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the actin cytoskeleton; a prerequisite for changes in cell shape and motility, and gene expression. Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signalling. More...
hsa04360	axon guidance	Axon guidance	Axon guidance represents a key stage in the formation of neu...... Axon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are read by growth cone receptors, and signal transduction pathways downstream of these receptors converge onto the Rho GTPases to elicit changes in cytoskeletal organization that determine which way the growth cone will turn. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05200	pathways in_cancer	Pathways in cancer
hsa04012	erbb signaling_pathway	ErbB signaling pathway	The ErbB family of receptor tyrosine kinases (RTKs) couples ...... The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase. More...
hsa04722	neurotrophin signaling_pathway	Neurotrophin signaling pathway	Neurotrophins are a family of trophic factors involved in di...... Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory. 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...
hsa04910	insulin signaling_pathway	Insulin signaling pathway	Insulin binding to its receptor results in the tyrosine phos...... Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK) and mitogenic responses in the form of gene transcription. SHC is another substrate of INSR. When tyrosine phosphorylated, SHC associates with GRB2 and can thus activate the RAS/MAPK pathway independently of IRS-1. More...
hsa05210	colorectal cancer	Colorectal cancer	Classically, colorectal cancer (CRC) has been believed to de...... Classically, colorectal cancer (CRC) has been believed to develop from normal mucosa through the premalignant adenoma by the step-wise accumulation of mutations. All CRC display either microsatellite instability (MSI) or chromosome instability (CIN). MSI occurs in 15% of colon cancers and results from inactivation of the DNA mismatch repair (MMR) system by either MMR gene mutations or hypermethylation of the MLH1 promoter. MSI promotes tumorigenesis through generating mutations in target genes that possess coding microsatellite repeats, such as beta-catenin, TGFBR2 and BAX. CIN is found in the majority of colon cancers and leads to a different pattern of gene alterations that contribute to tumor formation. Genes involved in CIN are those coding for APC, K-ras, SMAD4 and p53. More...
hsa04062	chemokine signaling_pathway	Chemokine signaling pathway	Inflammatory immune response requires the recruitment of leu...... Inflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for the cell trafficking and thus are vital for protective host response. In addition, chemokines regulate plethora of biological processes of hematopoietic cells to lead cellular activation, differentiation and survival. The chemokine signal is transduced by chemokine receptors (G-protein coupled receptors) expressed on the immune cells. After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. Various members of small GTPases are involved in this process. Induction of nitric oxide and production of reactive oxygen species are as well regulated by chemokine signal via calcium mobilization and diacylglycerol production. More...
hsa05217	basal cell_carcinoma	Basal cell carcinoma	The development of basal cell carcinoma is associated with c...... The development of basal cell carcinoma is associated with constitutive activation of sonic hedgehog signaling. Normally, ligand-dependent signaling by Hedgehog (Hh) homologs proceeds through binding to the Patched receptor. This binding relieves the Patched-mediated inhibition of signaling through the Smoothened (SMOH) gene product. This signaling ultimately results in the dissociation of the Gli1 transcription factor from an inhibitory complex in the cytoplasm, its subsequent translocation to the nucleus, and activation of target gene expression. The mutations in SMOH, PTCH1, and SHH in BCCs result in continuous activation of target genes. At a cellular level, sonic hedgehog signaling promotes cell proliferation. Mutations in TP53 are also found with high frequency (>50%) in sporadic BCC. More...
hsa04110	cell cycle	Cell cycle	Mitotic cell cycle progression is accomplished through a rep...... Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. 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...
hsa05010	alzheimers disease	Alzheimer's disease	Alzheimer's disease (AD) is a chronic disorder that slowly d...... Alzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specifically the more amyloidogenic form, Abeta42. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress. More...
hsa04310	wnt signaling_pathway	Wnt signaling pathway	Wnt proteins are secreted morphogens that are required for b...... Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin. More...
hsa04340	hedgehog signaling_pathway	Hedgehog signaling pathway	The Hedgehog (Hh) family of secreted signaling proteins play...... The Hedgehog (Hh) family of secreted signaling proteins plays a crucial role in development of diverse animal phyla, from Drosophila to humans, regulating morphogenesis of a variety of tissues and organs. Hh signaling is also involved in control of stem cell proliferation in adult tissues and aberrant activation of the Hh pathway has been linked to multiple types of human cancer. Members of the Hh family bind to patched (ptc), thus releasing smoothened (smo) to transduce a signal. Transcriptional activation occurs through the GLI family of proteins resulting in activation of target genes. More...
hsa04660	t cell_receptor_signaling_pathway	T cell receptor signaling pathway	Activation of T lymphocytes is a key event for an efficient ...... Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions, leading to T-cell proliferation, cytokine production and differentiation into effector cells. More...
hsa04662	b cell_receptor_signaling_pathway	B cell receptor signaling pathway	B cells are an important component of adaptive immunity. The...... B cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor (BCR) is an integral membrane protein complex that is composed of two immunoglobulin (Ig) heavy chains, two Ig light chains and two heterodimers of Ig-alpha and Ig-beta. After BCR ligation by antigen, three main protein tyrosine kinases (PTKs) -the SRC-family kinase LYN, SYK and the TEC-family kinase BTK- are activated. Phosphatidylinositol 3-kinase (PI3K) and phospholipase C-gamma 2 (PLC-gamma 2) are important downstream effectors of BCR signalling. This signalling ultimately results in the expression of immediate early genes that further activate the expression of other genes involved in B cell proliferation, differentiation and Ig production as well as other processes. More...
hsa05213	endometrial cancer	Endometrial cancer	Two types of endometrial carcinoma are distinguished with re...... Two types of endometrial carcinoma are distinguished with respect to biology and clinical course. Type-I carcinoma is related to hyperestrogenism by association with endometrial hyperplasia, frequent expression of estrogen and progesterone receptors and younger age, whereas type-II carcinoma is unrelated to estrogen, associated with atrophic endometrium, frequent lack of estrogen and progesterone receptors and older age. This classification has also been justified at the molecular level with Type 1 tumours being more commonly associated with abnormalities of DNA-mismatch repair genes, K-ras, PTEN and beta-catenin, and Type 2 tumours with abnormalities of p53 and HER2/neu. More...

GSK3B related BioCarta pathways (count: 12)

ID	Name	Brief Description	Full Description
Literature-origin BioCarta pathway
G1_PATHWAY	g1 pathway	Cell Cycle: G1/S Check Point	The G1/S cell cycle checkpoint controls the passage of eukar...... The G1/S cell cycle checkpoint controls the passage of eukaryotic cells from the first 'gap' phase (G1) into the DNA synthesis phase (S). Two cell cycle kinases, CDK4/6-cyclin D and CDK2-cyclin E, and the transcription complex that includes Rb and E2F are pivotal in controlling this checkpoint. During G1 phase, the Rb-HDAC repressor complex binds to the E2F-DP1 transcription factors, inhibiting the downstream transcription. Phosphorylation of Rb by CDK4/6 and CDK2 dissociates the Rb-repressor complex, permitting transcription of S-phase genes encoding for proteins that amplify the G1 to S phase switch and that are required for DNA replication. Many different stimuli exert checkpoint control including TGFb, DNA damage, contact inhibition, replicative senescence, and growth factor withdrawal. The first four act by inducing members of the INK4 or Kip/Cip families of cell cycle kinase inhibitors. TGFb additionally inhibits the transcription of Cdc25A, a phosphatase that activates the cell cycle kinases. Growth factor withdrawal activates GSK3b, which phosphorylates cyclin D, leading to its rapid ubiquitination and proteosomal degradation. Ubiquitination, nuclear export, and degradation are mechanisms commonly used to rapidly reduce the concentration of cell-cycle control proteins. More...

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
IGF1MTOR_PATHWAY	igf1mtor pathway	Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway	Skeletal muscle atrophies with disuse while with increased u...... Skeletal muscle atrophies with disuse while with increased use and increased load skeletal muscle exhibits hypertrophy, with an increase in the size of existing muscle fibers. One signaling pathway involved in regulating skeletal muscle atrophy and hypertrophy is the AKT/mTOR pathway. The mTOR pathway activity increases in response to muscle activity during hypertrophy and decreases in activity during atrophy. Blocking this pathway genetically or with the mTOR inhibitor rapamycin blocks hypertrophy and genetic activation of the pathway induces hypertrophy. One agent that promotes muscle hypertrophy is the growth factor IGF-1. IGF-1 activates AKT, GSK-3beta and mTOR to promote hypertrophy. In contrast, the calcineurin pathway is not involved in hypertrophy and is down-regulated by agents such as IGF-1 that promote hypertrophy. Calcineurin may modulate other aspects of muscle function such as the development of slow muscle fibers through transcriptional regulation. These pathways lead to regulation of protein translation, with increased translation apparently acting as a key regulatory point in skeletal muscle hypertrophy. Agents such as IGF-1 that stimulate skeletal muscle hypertrophy may provide treatments for muscle atrophy and wasting. More...
PITX2_PATHWAY	pitx2 pathway	Multi-step Regulation of Transcription by Pitx2	Many transcription factors play essential roles in normal de...... Many transcription factors play essential roles in normal development by determining the proliferation and differentiation of cells. The coordinated transcriptional control of proliferation in specific developmental cell types is crucial in multiple developmental settings. One of a family of three bicoid-related transcription factors, Pitx2 acts downstream of the extracellular signaling protein Wnt to drive proliferation of cells with specific developmental fates, including cells in the pituitary, cardiac outflow region, and muscle. Wnt binds to Frizzled, a G-protein coupled receptor, activating homologs of the Drosophila Disheveled protein. Activation of Frizzled and Disheveled inhibits the kinase GSK-3 beta, part of a protein complex in the absence of Wnt signaling, causing beta-catenin protein to accumulate in the cytoplasm. Beta-catenin is known to alter the function of transcription factors like TCF/Lef. One result of Wnt signaling is activation of the transcription factor Lef by beta-catenin, inducing Pitx2 expression. Wnt activation also changes Pitx2 from a repressor to an activator by causing transcriptional corepressors like histone deacetylase 1 (HDAC1) bound to Pitx2 to be exchanged for coactivators. With coactivators bound, Pitx2 activates transcription of genes that regulate the cell cycle like Cyclin D2. Different coactivators are recruited by Pitx2 and other transcription factors like Myc to the Cyclin D2 promoter, with CBP/p300 recruited first, followed by NLI/Ldb/CLIM, Tip60/TRRAP, and PBP coactivators. Many of these coactivators help to alter histone acetylation and chromatin structure as part of transcriptional activation. The activation of cell cycle genes by Pitx2 ultimately stimulates the proliferation of specific cell types with the confluence of tissue-specific gene expression, growth factor signaling and coactivator recruitment. More...
PS1_PATHWAY	ps1 pathway	Presenilin action in Notch and Wnt signaling	Presenilin-1 (PS1) is associated with gamma secretase activi...... Presenilin-1 (PS1) is associated with gamma secretase activity that cleaves amyloid precursor protein (APP) and is implicated in Alzheimer's disease. Presenilin-1 is also a component in gamma-secretase activity involved in signaling by the transmembrane protein Notch. Active gamma secretase requires PS-1 N-terminal fragment and a C-terminal fragment and is unique in catalyzing proteolysis within the transmembrane region of proteins. Other proteins such as nicastrin may also be components of the gamma-secretase. Binding of the ligand Delta by Notch appears to trigger two proteolytic cleavages of Notch. The first step cleaves an extracellular domain and is catalyzed by a metalloprotease termed alpha-secretase or TACE. The second cleavage step appears to occur within the transmembrane domain of Notch, and releases a Notch intracellular doman (NICD). Once released, NICD moves into the nucleus where it is involved in transcriptional regulation through CSL family transcription factors (CBF1, Su(H), Lag-1) or other transcriptional regulators such as LEF-1. Presenilin is also involved in the Wnt/frizzled signaling pathway through beta-catenin. Beta-catenin is a cytoskeletal component that enters the nucleus to act as a transcriptional cofactor. Binding of WNT to Frizzled causes disheveled (DSH) to inhibit Glycogen synthase kinase 3 beta (GSK-3b) activity. Phosphorylation of Beta-catenin induces the ubiquitination and proteolytic degradation of beta-catenin by the proteasome. Non-phosphorylated beta-catenin is stable and enters the nucleus to regulate transcription with TCF. The beta-catenin/TCF complex activates genes that promote cellular survival, proliferation and differentiation during development. Presenilin stimulates beta-catenin turnover, reducing its transcriptional activation. More...
EIF2_PATHWAY	eif2 pathway	Regulation of eIF2	Protein phosphorylation plays an important role in the contr...... Protein phosphorylation plays an important role in the control of translation by eukaryotic initiation factor-2 (eIF-2). eIF-2 binds GTP and Met-tRNAi and transfers the Met-tRNA to the 40S subunit, to form the 43S preinitiation complex. Later in the cycle, prior to elongation, the bound GTP is hydrolyzed , releasing eIF-2-GDP. For eIF-2 to promote another round of initiation, GDP must be exchanged for GTP, a reaction catalyzed by eIF-2B. Kinases activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2), and hemin deficiency (HRI) can phosphorylate the a subunit of eIF-2. This phosphorylation stabilizes the eIF-2-GDP-eIF-2B complex, inhibiting the turnover of eIF-2B. eIF-2B is also inhibited by GSK-3b phosphorylation. These events result in a shut-down of cellular protein synthesis and can lead to apoptosis. More...
NFAT_PATHWAY	nfat pathway	NFAT and Hypertrophy of the heart (Transcription in the broken heart)	Hypertrophy associated with both hypertension and obstructio...... Hypertrophy associated with both hypertension and obstruction to ventricular outflow leads to pathologic cardiac growth and it is associated with increase morbidity and mortality. Symptomatic ventricular disease takes a growing toll on the health of nations. As other cardiovascular diseases such as stroke and myocardial infraction are in decline as causes of mortality, the heart failure problem becomes increasingly urgent. Congenital heart defects occur in 1% of live births and fetal heart malformations are implicated in many pregnancies that end in still-birth or spontaneous abortion. The current paradigm suggests that the heart adapts to excess of hemodynamic loading by compensatory hypertrophy, which under condition of persistent stress, over time evolves into dysfunction and myocardial failure. There is considerable evidence that direct effects of increased mechanical stress are sensed within the ventricular wall and that signals critical for the generation of growth responses. Despite compelling statistics we still do not understand biochemically why heart defects are so prevalent. A single transcriptional regulator initially associated with the activation of the T-cells More...
PTDINS_PATHWAY	ptdins pathway	Phosphoinositides and their downstream targets.	Nine currently identified phosphoinositide 3-kinases (PI 3-K...... Nine currently identified phosphoinositide 3-kinases (PI 3-K) constitute a subfamily of lipid kinases that catalyze the addition of a phosphate molecule on the 3-position of the inositol ring of phosphoinositides. Phosphatidylinositol (PtdIns), the precursor of all phosphoinosi-tides (PI), constitutes less than 10% of the total lipid in eukaryotic cell membranes. Approximately 5% of cellular PI is phosphorylated at the 4-position (PtdIns-4-P), and another 5% is phosphorylated at both the 4- and 5-positions (PtdIns-4,5-P2 ). However, less than 0.25% of the total inositol-containing lipids are phosphorylated at the 3-position, consistent with the idea that these lipids exert specific regulatory functions inside the cell, as opposed to a structural function. Here we have chosen to highlight a group of the phosphoinositide targets of the PI3-Ks and their downstream targets. The downstream effects of these PI-3 targets are indicated in the lower band illustrating the important role the PI3Ks have in cell function and survival. More...
SHH_PATHWAY	shh pathway	Sonic Hedgehog (Shh) Pathway	Sonic Hedgehog (Shh) is one of a family of three secreted pr...... Sonic Hedgehog (Shh) is one of a family of three secreted proteins, including Indian Hedgehog (Ihh) and Desert Hedgehog (Dhh), that play distinct and crucial roles in development. The morphogenic signal Shh provides in the developing CNS induces proliferation of neuronal precursor cells in the developing cerebellum and other tissues. Proliferative signaling by Shh is involved in the development of cancer, including specific brain and skin cancers such as basal cell carcinomas, while activation of Shh signaling in neurons may also provide a means to induce neuronal regeneration. Mitogenic Shh signaling does not appear to involve Map kinase pathways, but may involve induction of Cyclin D1 expression to maintain Rb in the hyperphosphorylated state and allow progression through the G1 phase of the cell cycle. Activation of myc may be one mechanism by which Shh induces cell cycle progression. Activation of Shh proliferative signaling occurs through binding to a receptor complex including Patched (Ptc-1) and Smoothened, a G-protein coupled receptor. Patched is an integral membrane protein with twelve transmembrane domains that acts as an inhibitor of Smoothened activation. Patched has been classified as a tumor suppressor due to its inhibition of Smoothened and the presence of inactivated Ptc-1 mutations in some cancers. One possibility is that Ptc-1, which resembles transmembrane channels, may not directly associate with Smoothened but may repress Smoothened signaling by transporting an endogenous Smoothened inhibitor across the plasma membrane into the cytoplasm. Small non-peptidic agonists and antagonists of the Shh pathway have been identified and appear to act at the level of the Smoothened receptor, providing pharmacological tools to study Shh signaling. The pathway downstream of the Smoothened receptor has remained somewhat unclear, but involves the Gli family of transcriptional activators, including Gli-1, Gli-2, and Gli-3, homologs of the drosophila gene cubitis interruptis. Kinases including GSK-3 and PKA oppose activation of the Shh pathway, perhaps by regulating the stability of Shh pathway intermediate signaling factors transcription factors. Supressor of Fused (SUFU) interacts directly with Gli proteins, repressing Shh signaling while Dyrk1 is a kinase that acts by a distinct pathway to stimulate Gli1 activation of transcription. The multiplicity of factors involved in Shh signaling creates many opportunities for therapeutic intervention in the treatment of cancer and possibly neurodegenerative diseases. More...
WNT_PATHWAY	wnt pathway	WNT Signaling Pathway	Wnt family members are secreted glycoproteins who bind to ce...... Wnt family members are secreted glycoproteins who bind to cell surface receptors such as Frizzled. Wnt members can play a role in the expression of many genes by interacting with multiple disparate signaling pathways. Shown is the Wnt/beta-catenin pathway. More...
ALK_PATHWAY	alk pathway	ALK in cardiac myocytes	Heart formation is cued by a combination of positive and neg...... Heart formation is cued by a combination of positive and negative signals from surrounding tissues. Inhibitory signals that block heart formation in anterior paraxial mesoderm include Wnt family members expressed in dorsal neural tube and anti-BMPs expressed in the axial tissues (i.e., noggin in the notochord). Wnt signalling pathway, which is essential for setting up the entire body pattern during embryonic development involves glycogen synthase kinase-3 (GSK3). In the absence of Wnt signaling, GSK3 is active and phosphorylates b-catenin resulting in its degradation by ubiquitin-mediated proteolysis. Activation of Wnt signaling inhibits GSK3, thereby preventing phosphorylation of b-catenin, which is then able to move to the nucleus. There it associates with members of the LEF-1/TCF family of transcription factors, which activate the transcription of genes like cyclin-D1, myc, and MMPs. The Wnt signaling pathway is blocked by a family of secreted proteins such as crescent and Dkk-1 sufficient for induction of heart formation in posterior mesoderm. BMP signaling can also be blocked by the BMP antagonists noggin and chordin, which are secreted from the notochord and cooperate with Wnts to prevent cardiogenesis. Receptors for BMPs, members of the transforming growth factor-beta (TGFb) superfamily, are persistently expressed during cardiac development, yet mice lacking type II or type IA BMP receptors die at gastrulation and cannot be used to assess potential later roles in creation of the heart. Activin receptor-like kinase 3 (ALK3) is specifically required at mid-gestation for normal development of the trabeculae, compact myocardium, interventricular septum, and endocardial cushion. Cardiac muscle lacking ALK3 is specifically deficient in expressing TGFb2, an established paracrine mediator of cushion morphogenesis. In humans, congenital heart defects occur with a prevalence of at least 1% in newborns, and are even more common in death before term. Most frequent are defects in septation and the cardiac valves, and few single gene etiologies are known. The invariable defects in myocardium and AV cushion resulting from congenital deletion of ALK3 provide strong support for its assessment as a candidate gene in human congenital heart disease. More...
P35ALZHEIMERS_PATHWAY	p35alzheimers pathway	Deregulation of CDK5 in Alzheimers Disease	Cyclin-dependent kinase 5 (cdk5), a multi-functional kinase,...... Cyclin-dependent kinase 5 (cdk5), a multi-functional kinase, and its neuron-specific activator p35 are required for neurite outgrowth and cortical lamination. Proteolytic cleavage of p35 produces p25, which accumulates in the brains of patients with Alzheimer's disease. Conversion of p35 to p25 causes prolonged activation and mislocalization of cdk5 and the hyperphosphorylates tau, leading to the formation of paired helical filaments and promotes apoptosis. In cultured primary cortical neurons, excitotoxins, hypoxic stress and calcium influx induce the production of p25. In fresh brain lysates, addition of calcium can stimulate cleavage of p35 to p25. Specific inhibitors of calpain1, effectively inhibit the calcium-induced cleavage of p35. In vitro, calpain1 directly cleaves p35 to release a fragment with relative molecular mass 25,000. Application of the amyloid beta-peptide A beta induces the conversion of p35 to p25 in primary cortical neurons. Inhibition of cdk5 or calpain activity reduces cell death in A beta-treated cortical neurons. These observations indicate that cleavage of p35 to p25 by calpain may be involved in the pathogenesis of Alzheimer's disease. GSK3B also phosphoryklates tau but does not induce hyperphosphorylation in response to calpain activating stimuli. Additionally down-regulation or inhibition of PP2A increases the hyper-phosphorylation of tau. More...
GSK3_PATHWAY	gsk3 pathway	Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages	Lipopolysaccharide. One of the key actions of AKT is to bloc...... Lipopolysaccharide. One of the key actions of AKT is to block apoptosis. AKT phosphorylation of NF-kB promotes the survival and activation of macrophages responding to LPS. Another substrate of AKT is the protein kinase Gsk3-beta. AKT phosphorylates and deactivates Gsk3-beta. Non-phosphorylated Gsk3-beta is active and phosphorylates beta-catenin, leading to its degradation in the ubiquitin dependent proteosome pathway. Stimulation by LPS causes the accumulation of beta-catenin in the nucleus and the activation of genes in concert with the transcription factor LEF1. This pathway is probably not restricted to alveolar pathway, but leads to the activation of beta-catenin dependent genes by LPS in other cells as well. Other pathways regulate this pathway also, such as the modulation of PI3 kinase activity by ceramide, and the inhibition of Gsk3-beta activity by the Wnt/frizzled/disheveled (DSH) pathway. More...

GSK3B related Reactome pathways (count: 9)

ID	Name	Description
Gene mapped Reactome pathways
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_11065	betacatenin phosphorylation_cascade	Degradation of beta-catenin is initiated following amino-ter...... Degradation of beta-catenin is initiated following amino-terminal serine/threonine phosphorylation. Phosphorylation of B-catenin at S45 by CK1 alpha primes the subsequent sequential GSK-3-mediated phosphorylation at Thr41, Ser37 and Ser33. 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_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_19271	semaphorin interactions	Semaphorins are a large family of cell surface and secreted ...... Semaphorins are a large family of cell surface and secreted guidance molecules divided into eight classes on the basis of their structures. They all have an N-terminal conserved sema domain. Semaphorins signal through multimeric receptor complexes that include other proteins such as plexins and neuropilins. More...
REACT_19199	crmps in_sema3a_signaling	CRMPs are a small family of plexinA-interacting cytosolic ph...... CRMPs are a small family of plexinA-interacting cytosolic phosphoproteins identified as mediators of Sema3A signaling and neuronal differentiation. After Sema3A activation Plexin-A bound CRMP's undergo phosphorylation by Cdk5, GSK3beta and Fes kinases. Phosphorylation of CRMPs by these kinases blocks the ability of CRMP to bind to tubulin dimers, subsequently induces depolymerization of F-actin, and ultimately leads to growth cone collapse. More...
REACT_11045	signaling by_wnt	The beta-catenin destruction complex plays a key role in the...... The beta-catenin destruction complex plays a key role in the canonical Wnt signaling pathway. In the absence of Wnt signaling, this complex controls the levels of cytoplamic beta-catenin. Beta-catenin associates with and is phosphorylated by the destruction complex. Phosphorylated beta-catenin is recognized and ubiquitinated by the SCF-beta TrCP ubiquitin ligase complex and is subsequently degraded by the proteasome. More...
REACT_12564	akt phosphorylates_targets_in_the_cytosol	Following activation, AKT can phosphorylate an array of targ...... Following activation, AKT can phosphorylate an array of target proteins in the cytoplasm, many of which are involved in cell survival control. Phosphorylation of TSC2 feeds positively to the TOR kinase, which, in turn, contributes to AKT activation (positive feedback loop). 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...

GSK3B related interactors from protein-protein interaction data in HPRD (count: 74)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
GSK3B	GYS1	No	in vitro	6772446 , 11427888
GSK3B	SGK3	No	in vitro;in vivo;yeast 2-hybrid	12054501 , 16543730
GSK3B	CSDA	No	in vitro	16198352
GSK3B	CEBPA	No	in vivo	10567568
GSK3B	CREM	Yes	in vitro;in vivo	8404858
GSK3B	AURKA	No	in vitro	19060929
GSK3B	SGK1	No	in vitro;in vivo	16543730
GSK3B	PXN	No	in vivo	16537926
GSK3B	MARK2	No	in vitro	16257959
GSK3B	AR	Yes	in vitro;in vivo	15178691 , 15361837
GSK3B	CTNNB1	No	in vitro;in vivo	12051714 , 12000790 , 12114015 , 11818547
GSK3B	FOXO1	No	in vivo	11980723
GSK3B	MITF	No	in vitro	10587587
GSK3B	TP53	No	in vitro;in vivo	12048243 , 11483158 , 12064478
GSK3B	CCND1	Yes	in vitro;in vivo	9832503 , 10910956
GSK3B	MYC	No	in vitro;in vivo	11877389 , 8247524 , 16247449
GSK3B	PTK2	No	in vivo	11809746
GSK3B	AXIN2	No	in vitro;in vivo;yeast 2-hybrid	10966653 , 9566905
GSK3B	SNCAIP	No	in vitro;in vivo	16174773
GSK3B	BICD2	No	in vivo	17139249
GSK3B	FRAT2	No	in vitro	11738041
GSK3B	CDK5	No	in vitro	15652488
GSK3B	TMEM132A	No	in vivo	11524435
GSK3B	ACLY	No	in vitro	10653665
GSK3B	DNM1L	No	in vitro;yeast 2-hybrid	9731200
GSK3B	PRKCB	No	in vitro	1324914
GSK3B	NIN	No	yeast 2-hybrid	11004522
GSK3B	PRKACA	No	in vivo	12147701
GSK3B	GSK3B	Yes	in vitro	12554650
GSK3B	NFKB1	No	in vitro;in vivo	11425860
GSK3B	LRP6	No	in vitro	16365045
GSK3B	ILK	No	in vitro	9736715 , 16936772
GSK3B	TSC2	No	in vivo	12511557
GSK3B	DYNC1I1	Yes	in vivo	17139249
GSK3B	CABYR	No	in vitro	15752768
GSK3B	BCL3	No	in vitro;in vivo	15469820
GSK3B	TPPP	No	in vitro;in vivo	11781156
GSK3B	PTPN1	Yes	in vitro	7514173
GSK3B	CDH1	No	in vitro	10671552
GSK3B	HNRNPD	No	in vitro	12819195 , 11903055
GSK3B	MUC1	No	in vitro;in vivo	9819408
GSK3B	CREB1	Yes	in vivo	12162494
GSK3B	AKAP11	No	in vitro;in vivo;yeast 2-hybrid	12147701
GSK3B	PPP1R2	No	in vitro;in vivo	12761178 , 11320080
GSK3B	MCL1	No	in vitro;in vivo	16543145
GSK3B	AKT2	No	in vitro	12434148
GSK3B	YBX1	Yes	in vitro	16198352
GSK3B	UPF3A	No	yeast 2-hybrid	15231747
GSK3B	CTNND1	No	in vitro	12885254
GSK3B	DPYSL2	No	in vitro;in vivo	15652488
GSK3B	EIF2B5	No	in vitro;in vivo	11500362 , 15302935 , 9468292 , 12133000
GSK3B	APP	No	in vitro;in vivo	8764598 , 10936190 , 15178331
GSK3B	FRAT1	No	in vivo	12095675
GSK3B	NOTCH1	No	in vitro;in vivo	12123574
GSK3B	CDX2	No	in vitro	16027724
GSK3B	DCTN2	No	in vivo	17139249
GSK3B	PSEN1	Yes	in vivo	11104755 , 16814287
GSK3B	PPARGC1A	No	in vitro	18198341
GSK3B	SNAI1	No	in vivo	19004823
GSK3B	CCNE1	No	in vitro;in vivo	8861947 , 14536078
GSK3B	MAPT	No	in vitro	9832145 , 7566346 , 11181841 , 9771888 , 9199504 , 17078951
GSK3B	DCTN1	No	in vivo	17139249
GSK3B	E2F1	No	in vivo	18367454
GSK3B	NOTCH2	No	in vitro;in vivo	12794074
GSK3B	MAP1B	No	in vitro	9570753
GSK3B	PRKCZ	No	in vitro	11481324
GSK3B	IKBKG	No	in vitro	12808104
GSK3B	APC	Yes	in vitro	8638126 , 11166179
GSK3B	BICD1	No	in vitro;in vivo;yeast 2-hybrid	17139249
GSK3B	RCAN1	No	in vitro	12063245
GSK3B	AXIN1	No	in vitro;in vivo;yeast 2-hybrid	9482734 , 10488109 , 10581160 , 17318175 , 9734785
GSK3B	AKT1	No	in vitro;in vivo	11035810 , 8524413
GSK3B	OGT	No	in vitro;in vivo	10753899
GSK3B	MYOCD	No	in vitro;in vivo	16141410

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Literature-origin BioCarta pathway

Gene mapped BioCarta pathways

Gene mapped Reactome pathways