Gene Report

Basic Information

Approved Symbol	PTK2B
Approved Name	protein tyrosine kinase 2 beta
Previous Symbol	FAK2
Previous Name	protein tyrosine kinase 2 beta, "PTK2B protein tyrosine kinase 2 beta"
Symbol Alias	CAKB, PYK2, RAFTK, PTK, CADTK
Location	8p21.1
Position	chr8:27168999-27316908 (+)
External Links	Entrez Gene: 2185 Ensembl: ENSG00000120899 UCSC: uc003xfp.2 HGNC ID: 9612
No. of Studies (Positive/Negative)	2(2/0)
Type	Literature-origin

Positive relationships between PTK2B and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
PTK2B	Aston, 2005	patients and normal controls		Genes altered in major depressive disorder Genes altered in major depressive disorder
PTK2B	Klempan, 2009	patients and normal controls		Selected differentially expressed genes in BA44 to BA47 (ANO...... Selected differentially expressed genes in BA44 to BA47 (ANOVA and t-test P < 0.01, fold change 1.3t) More...

Positive relationships between PTK2B and other components at different levels (count: 0)

Positive relationship network of PTK2B in MK4MDD

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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 PTK2B and MDD (count: 0)

Negative relationships between PTK2B and other components at different levels (count: 0)

PTK2B related SNPs in MK4MDD (count: 0)

PTK2B related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Protein-tyrosine kinase 2-beta	Q14289	0(0/0)	Gene mapped

PTK2B related GO terms (count: 98)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006950	response to stress	biological process	TAS[8939945]
GO:0006915	apoptotic process	biological process	TAS[10880513]
GO:0000165	MAPK cascade	biological process	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0042220	response to cocaine	biological process	IEA
GO:0014069	postsynaptic density	cellular component	IEA
GO:0070098	chemokine-mediated signaling pathway	biological process	ISS
GO:0045453	bone resorption	biological process	ISS
GO:0048010	vascular endothelial growth factor receptor signaling pathway	biological process	IMP
GO:0005938	cell cortex	cellular component	IEA
GO:0030826	regulation of cGMP biosynthetic process	biological process	IEA
GO:0001954	positive regulation of cell-matrix adhesion	biological process	IMP[18765415]
GO:0010226	response to lithium ion	biological process	IEA
GO:0048041	focal adhesion assembly	biological process	IEA
GO:0005737	cytoplasm	cellular component	IDA
GO:0006970	response to osmotic stress	biological process	IEA
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation	biological process	IDA
GO:2000114	regulation of establishment of cell polarity	biological process	ISS
GO:0045860	positive regulation of protein kinase activity	biological process	IMP[7544443]
GO:0009612	response to mechanical stimulus	biological process	IEA
GO:0005925	focal adhesion	cellular component	IDA[18765415]
GO:0043267	negative regulation of potassium ion transport	biological process	IDA[7544443]
GO:0007166	cell surface receptor signaling pathway	biological process	IMP[8849729]
GO:0005634	nucleus	cellular component	IDA
GO:0070374	positive regulation of ERK1 and ERK2 cascade	biological process	IMP[7544443]
GO:0043149	stress fiber assembly	biological process	IEA
GO:0006468	protein phosphorylation	biological process	TAS[7529876]
GO:2000060	positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process	biological process	IEA
GO:0030307	positive regulation of cell growth	biological process	IEA
GO:0043507	positive regulation of JUN kinase activity	biological process	IEA
GO:0007172	signal complex assembly	biological process	IEA
GO:0043066	negative regulation of apoptotic process	biological process	IMP[19880522]
GO:0030502	negative regulation of bone mineralization	biological process	ISS
GO:0008360	regulation of cell shape	biological process	IMP[19086031]
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity	biological process	ISS
GO:0051000	positive regulation of nitric-oxide synthase activity	biological process	IEA
GO:0005886	plasma membrane	cellular component	IEA
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	IEA
GO:0009725	response to hormone stimulus	biological process	IEA
GO:0004871	signal transducer activity	molecular function	IEA
GO:0007165	signal transduction	biological process	TAS[7499242]
GO:0010595	positive regulation of endothelial cell migration	biological process	IDA
GO:2000538	positive regulation of B cell chemotaxis	biological process	ISS
GO:0043534	blood vessel endothelial cell migration	biological process	IEA
GO:0043423	3-phosphoinositide-dependent protein kinase binding	molecular function	IEA
GO:2000379	positive regulation of reactive oxygen species metabolic process	biological process	IEA
GO:0005829	cytosol	cellular component	TAS
GO:0032863	activation of Rac GTPase activity	biological process	IEA
GO:0046330	positive regulation of JNK cascade	biological process	IMP[8670418]
GO:2000058	regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process	biological process	IDA[19880522]
GO:0001556	oocyte maturation	biological process	IEA
GO:0048471	perinuclear region of cytoplasm	cellular component	IDA[18765415]
GO:0006461	protein complex assembly	biological process	TAS[10867021]
GO:0032960	regulation of inositol trisphosphate biosynthetic process	biological process	ISS
GO:0051279	regulation of release of sequestered calcium ion into cytosol	biological process	ISS
GO:0045121	membrane raft	cellular component	IEA
GO:0033209	tumor necrosis factor-mediated signaling pathway	biological process	IMP[8670418]
GO:0031175	neuron projection development	biological process	IEA
GO:0030838	positive regulation of actin filament polymerization	biological process	IMP[18765415]
GO:0032403	protein complex binding	molecular function	IEA
GO:0008285	negative regulation of cell proliferation	biological process	IMP[15050747]
GO:0050848	regulation of calcium-mediated signaling	biological process	IEA
GO:0018108	peptidyl-tyrosine phosphorylation	biological process	IDA[7544443]
GO:0030426	growth cone	cellular component	IEA
GO:0051591	response to cAMP	biological process	IEA
GO:0030335	positive regulation of cell migration	biological process	IMP[18765415]
GO:0010758	regulation of macrophage chemotaxis	biological process	ISS
GO:0042542	response to hydrogen peroxide	biological process	IEA
GO:0071300	cellular response to retinoic acid	biological process	IMP[17910947]
GO:0010976	positive regulation of neuron projection development	biological process	IMP[17910947]
GO:0042493	response to drug	biological process	IEA
GO:0005515	protein binding	molecular function	IPI[18086875]
GO:0045471	response to ethanol	biological process	IEA
GO:0002315	marginal zone B cell differentiation	biological process	ISS
GO:0007204	elevation of cytosolic calcium ion concentration	biological process	IEA
GO:0030424	axon	cellular component	IEA
GO:0014009	glial cell proliferation	biological process	IEA
GO:0010752	regulation of cGMP-mediated signaling	biological process	IEA
GO:0046777	protein autophosphorylation	biological process	TAS[8849729]
GO:2000249	regulation of actin cytoskeleton reorganization	biological process	ISS
GO:0002040	sprouting angiogenesis	biological process	ISS
GO:0051592	response to calcium ion	biological process	IEA
GO:0005524	ATP binding	molecular function	IEA
GO:0045638	negative regulation of myeloid cell differentiation	biological process	IMP[15050747]
GO:0045766	positive regulation of angiogenesis	biological process	IEA
GO:0042976	activation of Janus kinase activity	biological process	IMP[8670418]
GO:0001666	response to hypoxia	biological process	IEA
GO:0005730	nucleolus	cellular component	IDA
GO:0045428	regulation of nitric oxide biosynthetic process	biological process	IEA
GO:0004713	protein tyrosine kinase activity	molecular function	TAS[8939945]
GO:0007229	integrin-mediated signaling pathway	biological process	IMP[15050747]
GO:0030027	lamellipodium	cellular component	IDA[18765415]
GO:0008284	positive regulation of cell proliferation	biological process	IMP[18765415]
GO:0004715	non-membrane spanning protein tyrosine kinase activity	molecular function	IDA[7544443]
GO:0045727	positive regulation of translation	biological process	IEA
GO:0009749	response to glucose stimulus	biological process	IEA
GO:0030155	regulation of cell adhesion	biological process	IMP[19086031]

PTK2B related KEGG pathways (count: 5)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04020	calcium signaling_pathway	Calcium signaling pathway	Ca2+ that enters the cell from the outside is a principal so...... Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM). More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
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...
hsa04670	leukocyte transendothelial_migration	Leukocyte transendothelial migration	Leukocyte migaration from the blood into tissues is vital fo...... Leukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (CAM) and then migrate across the vascular endothelium. A leukocyte adherent to CAMs on the endothelial cells moves forward by leading-edge protrusion and retraction of its tail. In this process, alphaL /beta2 integrin activates through Vav1, RhoA, which subsequently activates the kinase p160ROCK. ROCK activation leads to MLC phosphorylation, resulting in retraction of the actin cytoskeleton. Moreover, Leukocytes activate endothelial cell signals that stimulate endothelial cell retraction during localized dissociation of the endothelial cell junctions. ICAM-1-mediated signals activate an endothelial cell calcium flux and PKC, which are required for ICAM-1 dependent leukocyte migration. VCAM-1 is involved in the opening of the endothelial passage through which leukocytes can extravasate. In this regard, VCAM-1 ligation induces NADPH oxidase activation and the production of reactive oxygen species (ROS) in a Rac-mediated manner, with subsequent activation of matrix metallopoteinases and loss of VE-cadherin-mediated adhesion. More...
hsa04912	gnrh signaling_pathway	GnRH signaling pathway	Gonadotropin-releasing hormone (GnRH) secretion from the hyp...... Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes. More...
hsa04650	natural killer_cell_mediated_cytotoxicity	Natural killer cell mediated cytotoxicity	Natural killer (NK) cells are lymphocytes of the innate immu...... Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. This inhibitory signal is lost when the target cells do not express MHC class I and perhaps also in cells infected with virus, which might inhibit MHC class I exprssion or alter its conformation. The mechanism of NK cell killing is the same as that used by the cytotoxic T cells generated in an adaptive immune response; cytotoxic granules are released onto the surface of the bound target cell, and the effector proteins they contain penetrate the cell membrane and induce programmed cell death. More...

PTK2B related BioCarta pathways (count: 10)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
MET_PATHWAY	met pathway	Signaling of Hepatocyte Growth Factor Receptor	The hepatocyte growth factor receptor, also called c-Met, is...... The hepatocyte growth factor receptor, also called c-Met, is activated by HGF and stimulates proliferation of hepatocytes and other cell types. Mutated forms of the HGF receptor are associated with oncogenesis and metastasis, making the HGF receptor a potential therapeutic target for cancer drugs. Changes in cell motility, cell shape, adhesion, resistance to apoptosis, and anchorage independent growth all contribute to the role of c-Met in cancer. The HGF receptor is a heterodimer with tyrosine kinase activity and associates with a multiprotein complex involved in downstream signal transduction. The HGF receptor can associate with several different signaling systems, including src, Grb2/SOS, PI3 kinase and Gab1. One of the major substrates of the activated HGF receptor tyrosine kinase is the adaptor protein Gab1. Gab1 interacts with Crk and CrkL, two proteins with SH2 and SH3 protein interaction domains that couple to signaling further downstream. The actions of HGF on paxillin, DOCK180 and Rap1 mediated through GAB1 and other members of this complex alter cell motility. Regulation of Rho, Rac1 and CDC42 pathways in response to HGF all contribute to changes in cellular motility. Another target of the HGF receptor kinase is the focal adhesion kinase, FAK. The activation of FAK induces the formation of focal adhesions, a preliminary step to increased cell motility and tissue invasion by transformed cells, and paxillin phosphorylation may also alter cell adhesion of Met transformed cells. Src and p130cas are required for the role of FAK in HGF induced cellular transformation. HGF also blocks anoikis, the induction of apoptosis through suspension of cells, by acting on Erk and AKT kinases. This activity may contribute to anchorage independent growth of Met transformed cells. Signaling by integrins also plays a key role in the activation of tissue invasive growth by HGF. The alpha6beta4 integrin acts as a cofactor along with Meta to participate in cell growth and proliferation. In addition to altering cell adhesion, proliferation and cell motility, HGF alters cellular transcription through activation of STAT3. STAT3 activation by HGF is independent of PI3 kinase or map kinases and alters gene expression leading to changes in cellular shape. Although HGF is associated with cellular proliferation and survival, in rat liver epithelial cells HGF induces apoptosis and inhibits cell growth. More...
ACH_PATHWAY	ach pathway	Role of nicotinic acetylcholine receptors in the regulation of apoptosis	Nicotinic acetylcholine receptors are essential for neuromus...... Nicotinic acetylcholine receptors are essential for neuromuscular signaling and are also expressed in non-neuronal tissues, where their function is less clear. Although nicotinic acetylcholine receptors are primarily known for their action as ligand-gated ion channels transducing action potentials across synapses, they may have other actions. Nicotinic acetylcholine receptors in neurons alter apoptotic signaling, protecting against cell death in some settings, and this action may in some cases be directed through alternative signaling pathways. In neurons the alpha-7 nicotinic receptor activates PI3 kinase through a src-family kinase, activating the anti-apoptotic kinase AKT. One pathway involved in AKT signaling involves phosphorylation of the forkhead transcription factor FKHRL1, causing its retention in the cytoplasm associated with 14-3-3, and blocking expression of the apoptotic fas protein. The PI3 kinase/AKT pathway protects a broad range of neurons against apoptotic cell death and may block apoptosis triggered by beta-amyloid fragments that contributes to the progression of Alzheimers disease. If so, nicotinic agents may prove useful in the treatment of this and other neurodegenerative conditions. There are several proteins that modulate the response of nicotinic acetylcholine receptors, include synapse formation. Prior to synapse formation, nicotinic receptors are randomly dispersed in the post-synaptic membrane. A neuronal protein, agrin, binds to the Musk receptor in the muscle membrane, stimulating clustering of nicotinic receptors and synapse formation. Rapsyn is present at high levels at synapses with nicotinic receptors, bringing them together at high densities and anchoring clustered receptors to the cytoskeleton. Members of the Src family of tyrosine kinases also play a role in clustering caused by Rapsyn, phosphorylating the nicotinic receptors, rapsyn, and other targets. Nicotinic receptors expressed in non-neuronal tissues may also be involved in the response to smoking. In lung epithelial cells, nicotine from cigarette smoke blocks apoptosis by activating the anti-apoptotic kinase AKT, contributing perhaps to carcinogenesis and resistance to chemotherapy. Activation of nicotinic acetylcholine receptors in dermal fibroblasts may contribute to the altered wound healing and skin elasticity related to smoking. Activation of keratinocyte nicotinic receptors may also alter the properties of skin. More...
PYK2_PATHWAY	pyk2 pathway	Links between Pyk2 and Map Kinases	This diagram is a compilation of Pyk2 effort cascades. In sp...... This diagram is a compilation of Pyk2 effort cascades. In specific cell types the receptor and effoectors will vary. Binding of a transmembrane receptor triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to Pyk2 and further to the small G protein Rac1. In turn, Rac1 initiatates the JNK cascade, starting with PAK follwed by MEKK1, SEK1, and JNK. JNK activation causes induction of c-Jun gene binding. Pyk2 stimulation has also been shown to activate MKK3 leading to activation of p38. The other major mitogen activated kinase cascade for ERK1/2 is stimulated via RAS, RAF and MEKK1/2. More...
IL7_PATHWAY	il7 pathway	IL-7 Signal Transduction	IL-7 is a key cytokine in the immune system, essential for n...... IL-7 is a key cytokine in the immune system, essential for normal development of B cells and T cells. Mice with the IL-7 receptor deleted lack B and T cells. Some humans with SCID (severe combined immunodeficiency disease) also have mutation of their IL-7 receptor gene leading to an absence of T cells and greatly impaired B cell production. The IL-7 receptor includes two polypeptides, a gamma chain and an alpha chain. The alpha-chain is unique to the IL-7 receptor while several other cytokines use the same gamma receptor chain as IL-7, including IL-2, IL-4, IL-9, IL-15 and IL-21. Binding of IL-7 to the alpha chain leads to dimerization of the alpha and gamma chains. JAK3 associated with the gamma chain tyrosine phosphorylates the alpha chain after dimerization. The importance of JAK3 in IL-7 signaling is supported by the similarity of the immune defects in JAK3 knockout mice and IL-7 knockout mice. The phosphorylated alpha chain serves as the site for recruiting other signaling molecules to the complex to be phosphorylated and activated, including STAT5, src kinases, PI3 kinase, Pyk2 and Bcl2 proteins. Some targets of IL-7 signaling contribute to cellular survival, including Bcl2 and Pyk2. Other targets contribute to cellular proliferation, including PI3 kinase, src family kinases (lck and fyn) and STAT5. The transcription factor STAT5 contributes to activation of multiple different downstream genes in B and T cells and may contribute to VDJ recombination through alteration of chromatin structure. The cell survival and cell proliferation signals induced by IL-7 combine to induce normal B and T cell development. More...
AT1R_PATHWAY	at1r pathway	Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling	Ang II binding to AT1-R triggers the activation of Ca2+ sign...... Ang II binding to AT1-R triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to the Pyk2 and further to the small G protein Rac1 but not Cdc42, although the direct activation of Rac1 by Pyk2 is not proved in this study. In turn, Rac1 activates a small G protein-activated kinase whose identity is still controversial, but one of which has been suggested to be PAK1. Finally, the JNK cascade, including MEKK1, SEK1, and JNK, is activated, causing induction of c-Jun gene via binding of ATF2 and c-Jun heterodimer to the junTRE2 site. Ang II is closely involved in the cardiac remodeling by stimulating synthesis of extracellular matrix proteins. It was recently found that expression of fibronectin by Ang II is transcriptionally regulated by AP-1 complex in cardiac fibroblasts. Collagenase gene containg AP-1 sites is also regulated by AP-1 components including c-Jun. AP-1 activity is also enhanced in Ang II-induced cardiac hypertrophy. Expression of ANF is regulated by AP-1 components. More...
CCR5_PATHWAY	ccr5 pathway	Pertussis toxin-insensitive CCR5 Signaling in Macrophage	The chemokine receptors CCR5 and CXCR4 in macrophages are ac...... The chemokine receptors CCR5 and CXCR4 in macrophages are activated by their peptide ligands and also by the HIV envelope protein GP120 during HIV infection. One mechanism of signaling by these GPCRs is through activation of Gi signaling. These chemokine receptors can also signal through a Gi-independent pertussis toxin-insensitive pathway. This pathway elevates calcium influx into the cell through CRAC channels, ion channels that are activated by calcium release. Elevated calcium from CRAC is required for downstream activation of Pyk2, a focal adhesion-associated protein kinase. Non Gi signaling by these chemokine receptors also involves the Jnk and p38 Map kinase pathways leading to AP-1 activation and activation of genes such as MIP-1 and MCP-1. This pathway may be involved in the role of macrophages in the pathogenesis of AIDS. More...
PAR1_PATHWAY	par1 pathway	Thrombin signaling and protease-activated receptors	Thrombin is an extracellular protease that is involved in th...... Thrombin is an extracellular protease that is involved in the clotting of blood and inflammation through its action on platelets and endothelial cells in the vasculature and that plays a role in thrombosis and myocardial infarction. The protease activated receptors PAR1 and PAR4 are cellular targets of thrombin signaling and members of the G-protein coupled receptor gene family. Both of these receptors are cleaved in their N-terminus by thrombin, unmasking a portion of the receptor sequence that acts itself as a tethered peptide ligand that activates the receptor. The tethered ligand that activates PAR1 is SFLLRN and the tethered ligand that activates PAR4 is GYPGQV. Other members of the family include PAR2 which is activated by trypsin rather than thrombin and PAR3 which seems to play a role in the activation of other PARs but does not itself transduce a signal directly. Addition of peptide agonist exogenously in solution can also activate PAR1, PAR2 and PAR4. PAR1 activation may be involved in the dilation of arteries during inflammation through the action of thrombin on endothelial cells and in platelet activation by thrombin during clotting. PAR1 and PAR2 activation cause bronchodilation in airway and may protect against asthma. PAR 4 activation by thrombin activates platelets during clotting and mice lacking PAR4 have impaired clotting and platelets that do not respond to thrombin signaling. The action of thrombin on PAR1 and PAR4 on platelets and endothelial cells may also contribute to vascular permeability and inflammation. Activated PARs appear to couple primarily through Gq-mediated stimulation of inositol phosphate metabolism and intracellular calcium levels to activate platelets. PAR1 and PAR4 also appear to couple to multiple G-proteins and transduce signals through more than one G-protein mediated pathway in some circumstances. Signaling by PAR1 and PAR4 through Galpha12 pathways couples to Rho signaling and changes in cytoskeletal structure and cell shape. Gi activation does not appear necessary for platelet activation by PAR1 or PAR4, and platelet activation by these receptors requires an ADP signal perhaps acting through the platelet-associated purinergic receptor P2Y12. Gi-coupled signaling may play a role in mitogenic PAR signaling in some settings through Map kinase activation. Activation of Rho by PAR1 can induce cellular transformation through a Galpha12 mediated mechanism and sustained rho-dependent phosphorylation of the myosin light chain by PAR1 contributes to cytoskeletal changes and activation of platelets. Since the activation of PARs by protease cleavage is irreversible the primary mechanism for down-regulation of the PAR signaling cascade appears to be internalization and degradation of PAR receptors. More...
NKCELLS_PATHWAY	nkcells pathway	Ras-Independent pathway in NK cell-mediated cytotoxicity	NK (natural killer) cells are lymphocytes distinct from B an...... NK (natural killer) cells are lymphocytes distinct from B and T cells that induce perforin-mediated lysis of tumor cells and virus-infected cells. NK cell-mediated cytotoxicity is activated by glycoproteins on the cell surface (activating receptors) and inhibited by MHC-1 with self-peptide bound. The MHC-1 inhibitory signal through Ig-family or lectin receptors prevents NK cells from killing normal cells. Abnormal MHC-1 expression in infected or tumor cells results in the release of perforin, the lysis of the abnormal cell and the release of cytokines that stimulate the immune response. MAP kinase inhibitors but not ras inhibitors are able to block NK cell cytotoxicity, indicating that the pathway can function by a ras-independent manner that involves the MAP kinase pathway. This pathway includes phosphoinositide-3-kinase (PI3K) as a key component, followed by Rac1 and the exchange factor Vav. The tyrosine kinase SYK and LAT may provide an additional pathway for activation of MAP kinases leading to NK cell activation, and also Pyk-2 activation by integrins. The protein tyrosine phosphatase SHP-1 appears to mediate the cytotoxicity inhibitory signal that blocks lysis of normal cells. The balance of these positive and negative signaling pathways regulates the role of NK cells in the immune response. More...
CXCR4_PATHWAY	cxcr4 pathway	CXCR4 Signaling Pathway	CXCR4 is a chemokine receptor in the GPCR gene family, and i...... CXCR4 is a chemokine receptor in the GPCR gene family, and is expressed by cells in the immune system and the central nervous system. In response to binding its ligand SDF-1 (stromal cell-derived factor-1), CXCR4 triggers the migration and recruitment of immune cells. This ligand-receptor pair may also play a role in development of the nervous system. In addition to acting as a chemokine receptor, CXCR4 is a co-receptor for entry of HIV into T cells and ligands of CXCR4, including SDF-1 may help to block HIV infection. Early in the infection of an individual, HIV viruses often are tropic for the CCR5 coreceptor that provides for macrophage entry, then later in infection are tropic for CXCR4 and T cell entry. Viruses that are tropic for CXCR4 are generally syncitium forming, causing T cells to aggregate and be destroyed at a rapid rate. CXCR4 induces downstream signaling by several different pathways. As a GPCR, CXCR4 binding of SDF-1 activates G-protein mediated signaling, including downstream pathways such as ras, and PI3 kinase. PI3 kinase activated by SDF-1 and CXCR4 plays a role in lymphocyte chemotaxis in response to these signals. One endpoint of CXCR4 signaling is the activation of transcription factors such as AP-1 and chemokine regulated genes. JAK/STAT signaling pathways also appear to play a role in SDF-1/CXCR4 signaling. Delineation of the signaling mechanisms utilized by CXCR4 may assist in determining the role of CXCR4 in HIV infection and in the immune response. More...
BIOPEPTIDES_PATHWAY	biopeptides pathway	Bioactive Peptide Induced Signaling Pathway	Many different peptides act as signaling molecules, includin...... Many different peptides act as signaling molecules, including the proinflammatory peptide bradykinin, the protease enzyme thrombin, and the blood pressure regulating peptide angiotensin. While these three proteins are distinct in their sequence and physiology, and act through different cell surface receptors, they share in a common class of cell surface receptors called G-protein coupled receptors (GPCRs). Other polypeptide ligands of GPCRs include vasopressin, oxytocin, somatostatin, neuropeptide Y, GnRH, leutinizing hormone, follicle stimulating hormone, parathyroid hormone, orexins, urotensin II, endorphins, enkephalins, and many others. GPCRs are a broad and diverse gene family that respond not only to peptide ligands but also small molecule neurotransmitters (acetylcholine, dopamine, serotonin and adrenaline), light, odorants, taste, lipids, nucleotides, and ions. The main signaling mechanism used by GPCRs is to interact with G-protein GTPase proteins coupled to downstream second messenger systems including intracellular calcium release and cAMP production. The intracellular signaling systems used by peptide GPCRs are similar to those used by all GPCRs, and are typically classified according to the G-protein they interact with and the second messenger system that is activated. For Gs-coupled GPCRs, activation of the G-protein Gs by receptor stimulates the downstream activation of adenylate cyclase and the production of cyclic AMP, while Gi-coupled receptors inhibit cAMP production. One of the key results of cAMP production is activation of protein kinase A. Gq-coupled receptors stimulate phospholipase C, releasing IP3 and diacylglycerol. IP3 binds to a receptor in the ER to cause the release of intracellular calcium, and the subsequent activation of protein kinase C, calmodulin-dependent pathways. In addition to these second messenger signaling systems for GPCRs, GPCR pathways exhibit crosstalk with other signaling pathways including tyrosine kinase growth factor receptors and map kinase pathways. Transactivation of either receptor tyrosine kinases like the EGF receptor or focal adhesion complexes can stimulate ras activation through the adaptor proteins Shc, Grb2 and Sos, and downstream Map kinases activating Erk1 and Erk2. Src kinases may also play an essential intermediary role in the activation of ras and map kinase pathways by GPCRs. More...

PTK2B related Reactome pathways (count: 0)

PTK2B related interactors from protein-protein interaction data in HPRD (count: 68)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
PTK2B	ERBB2	No	in vivo	10713673
PTK2B	DLG4	Yes	in vitro;in vivo	12576483
PTK2B	PIK3R1	Yes	in vivo	10797305
PTK2B	KCNA2	No	in vivo	11739373
PTK2B	DLGAP3	No	in vitro	16202977
PTK2B	RB1CC1	No	in vitro;in vivo;yeast 2-hybrid	10769033
PTK2B	RASA1	No	in vivo	10713673
PTK2B	FGFR2	Yes	in vitro;in vivo	15105428
PTK2B	PDCD6IP	No	in vivo	15557335
PTK2B	LCK	No	in vitro;in vivo	9091579
PTK2B	SRC	No	in vitro;in vivo	8849729 , 10777553
PTK2B	PITPNM1	No	in vitro;in vivo;yeast 2-hybrid	10022914
PTK2B	ZAP70	No	in vivo	10867021
PTK2B	JAK1	No	in vitro;in vivo	10702271
PTK2B	SLC2A1	No	in vivo	11007796
PTK2B	GSN	No	in vitro;in vivo;yeast 2-hybrid	12578912
PTK2B	JAK2	No	in vivo	11818507
PTK2B	BCAR1	No	in vivo	8995252
PTK2B	PTK2	No	in vitro	16760434
PTK2B	MYH2	No	in vitro	10082674
PTK2B	ITGB3	No	in vitro;in vivo	11683411
PTK2B	PITPNM3	No	in vitro;in vivo;yeast 2-hybrid	10022914
PTK2B	JAK3	No	in vitro	9512511
PTK2B	NPHP1	No	in vitro;in vivo	11493697
PTK2B	SNCA	No	in vitro;in vivo	12096713 , 11744621 , 11162638
PTK2B	MAP3K4	No	in vitro	15881658
PTK2B	PITPNM2	No	in vitro;in vivo;yeast 2-hybrid	10022914
PTK2B	FGFR3	Yes	in vitro;in vivo	15105428
PTK2B	PXN	No	in vitro	9099734
PTK2B	GRB2	No	in vivo	10354709 , 10329689
PTK2B	CBL	No	in vivo	11149930
PTK2B	LPXN	No	in vivo	9565592
PTK2B	SYK	No	in vivo	10747947
PTK2B	ITGB2	No	in vitro;in vivo	10961871
PTK2B	IL7R	No	in vivo	10702271
PTK2B	ASAP2	No	in vitro;in vivo	10022920
PTK2B	TLN1	No	in vivo	9442086
PTK2B	SH2D3C	No	in vitro;in vivo	12486027
PTK2B	EWSR1	No	in vitro;in vivo	10322114
PTK2B	STAP1	No	in vitro	10518561
PTK2B	ARHGAP5	No	in vivo	10713673
PTK2B	PTPN11	No	in vitro;in vivo	10880513
PTK2B	STAT3	No	in vitro	14963038
PTK2B	MATK	No	in vitro;in vivo	12063569
PTK2B	PTPN12	No	in vitro;in vivo	11337490 , 12231407 , 15588985
PTK2B	MCAM	No	in vitro	11036077
PTK2B	PTPN6	Yes	in vitro;in vivo	10521452 , 10747947
PTK2B	ARHGAP21	No	in vitro;in vivo;yeast 2-hybrid	11238453
PTK2B	CRK	No	in vitro;in vivo	10329689
PTK2B	CCR5	No	in vivo	9446638
PTK2B	VAV1	No	in vitro;in vivo	10867021
PTK2B	TGFB1I1	No	in vitro;in vivo	9422762 , 11856738 , 11937718
PTK2B	ASAP1	No	in vitro;in vivo;yeast 2-hybrid	12771146
PTK2B	GNA13	No	in vitro;in vivo	10821841
PTK2B	SHC1	No	in vitro;in vivo	7544443
PTK2B	PRKCD	No	in vivo	11352632
PTK2B	PDPK1	No	in vivo	14585963
PTK2B	ERBB3	Yes	in vitro	15499613
PTK2B	FYN	No	in vitro;in vivo	9091579 , 10867021 , 9104812
PTK2B	DLG3	No	in vitro;in vivo	12576483
PTK2B	EGFR	No	in vivo	10777553
PTK2B	LYN	No	in vivo	11311138
PTK2B	GRIN2A	Yes	in vivo	11478920
PTK2B	PTK2B	Yes	in vitro;in vivo	11493697 , 9560226 , 11337490
PTK2B	NEDD9	No	in vivo	9020138
PTK2B	FLT1	No	in vivo	11751905
PTK2B	EFS	Yes	in vitro	9750131
PTK2B	SORBS2	Yes	in vitro	15128873

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped BioCarta pathways