PTK2B

Protein tyrosine kinase 2 beta

Rendering based on PDB 2FO6.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2FO6, 2LK4, 3CC6, 3ET7, 3FZO, 3FZP, 3FZR, 3FZS, 3FZT, 3GM1, 3GM2, 3GM3, 3H3C, 3U3F, 4EKU, 4H1J, 4H1M, 4R32

Identifiers

Symbols

PTK2B ; CADTK; CAKB; FADK2; FAK2; PKB; PTK; PYK2; RAFTK

External IDs

OMIM: 601212 MGI: 104908 HomoloGene: 23001 ChEMBL: 5469 GeneCards: PTK2B Gene

EC number

2.7.10.2

Gene ontology
Molecular function	• calmodulin-dependent protein kinase activity • protein tyrosine kinase activity • non-membrane spanning protein tyrosine kinase activity • signal transducer activity • NMDA glutamate receptor activity • receptor binding • protein binding • ATP binding • protein complex binding • 3-phosphoinositide-dependent protein kinase binding
Cellular component	• nucleus • nucleoplasm • cytoplasm • cytosol • cytoskeleton • focal adhesion • cell cortex • postsynaptic density • NMDA selective glutamate receptor complex • lamellipodium • axon • dendrite • growth cone • extrinsic component of cytoplasmic side of plasma membrane • neuronal cell body • cell body • membrane raft • perinuclear region of cytoplasm • apical dendrite
Biological process	• MAPK cascade • angiogenesis • oocyte maturation • response to hypoxia • positive regulation of cell-matrix adhesion • sprouting angiogenesis • adaptive immune response • marginal zone B cell differentiation • protein complex assembly • protein phosphorylation • apoptotic process • response to stress • cellular defense response • response to osmotic stress • cytoskeleton organization • cell adhesion • signal transduction • cell surface receptor signaling pathway • signal complex assembly • epidermal growth factor receptor signaling pathway • positive regulation of cytosolic calcium ion concentration • integrin-mediated signaling pathway • positive regulation of cell proliferation • negative regulation of cell proliferation • regulation of cell shape • response to mechanical stimulus • response to hormone • response to glucose • response to lithium ion • positive regulation of endothelial cell migration • negative regulation of muscle cell apoptotic process • regulation of cGMP-mediated signaling • regulation of macrophage chemotaxis • positive regulation of neuron projection development • glial cell proliferation • cell migration • peptidyl-tyrosine phosphorylation • cell differentiation • regulation of cell adhesion • positive regulation of cell growth • positive regulation of cell migration • negative regulation of bone mineralization • regulation of cGMP biosynthetic process • positive regulation of actin filament polymerization • neuron projection development • regulation of inositol trisphosphate biosynthetic process • tumor necrosis factor-mediated signaling pathway • ionotropic glutamate receptor signaling pathway • response to immobilization stress • peptidyl-tyrosine autophosphorylation • response to cocaine • response to drug • response to hydrogen peroxide • activation of Janus kinase activity • negative regulation of apoptotic process • stress fiber assembly • negative regulation of potassium ion transport • positive regulation of JUN kinase activity • negative regulation of neuron apoptotic process • blood vessel endothelial cell migration • positive regulation of phosphatidylinositol 3-kinase activity • innate immune response • regulation of nitric oxide biosynthetic process • bone resorption • response to ethanol • negative regulation of myeloid cell differentiation • positive regulation of translation • positive regulation of angiogenesis • positive regulation of protein kinase activity • positive regulation of JNK cascade • protein autophosphorylation • vascular endothelial growth factor receptor signaling pathway • focal adhesion assembly • positive regulation of peptidyl-tyrosine phosphorylation • regulation of calcium-mediated signaling • positive regulation of nitric-oxide synthase activity • regulation of release of sequestered calcium ion into cytosol • response to cAMP • response to calcium ion • positive regulation of synaptic transmission, glutamatergic • long-term synaptic potentiation • chemokine-mediated signaling pathway • positive regulation of ERK1 and ERK2 cascade • cellular response to retinoic acid • cellular response to fluid shear stress • activation of GTPase activity • regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • regulation of establishment of cell polarity • regulation of actin cytoskeleton reorganization • regulation of N-methyl-D-aspartate selective glutamate receptor activity • positive regulation of reactive oxygen species metabolic process • positive regulation of excitatory postsynaptic potential • positive regulation of B cell chemotaxis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 8:
27.31 – 27.46 Mb

Chr 14:
66.15 – 66.28 Mb

PubMed search

Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.^[1]^[2]

Function

This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity.^[3]

The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation.^[3]

This protein has been shown to bind a CRK-associated substrate, a nephrocystin, a GTPase regulator associated with FAK, and the SH2 domain of GRB2.^[3]

The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Four transcript variants encoding two different isoforms have been found for this gene.^[3]

Interactions

PTK2B has been shown to interact with:

References

↑ Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J (September 1995). "Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions". Nature 376 (6543): 737–45. doi:10.1038/376737a0. PMID 7544443.
↑ Avraham S, London R, Fu Y, Ota S, Hiregowdara D, Li J, Jiang S, Pasztor LM, White RA, Groopman JE (1995). "Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain". J. Biol. Chem. 270 (46): 27742–51. doi:10.1074/jbc.270.46.27742. PMID 7499242.
1 2 3 4 "Entrez Gene: PTK2B PTK2B protein tyrosine kinase 2 beta".
↑ Manié SN, Beck AR, Astier A, Law SF, Canty T, Hirai H, Druker BJ, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin JD, Golemis EA, Freedman AS (February 1997). "Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells". J. Biol. Chem. 272 (7): 4230–6. doi:10.1074/jbc.272.7.4230. PMID 9020138.
1 2 Anfosso F, Bardin N, Vivier E, Sabatier F, Sampol J, Dignat-George F (January 2001). "Outside-in signaling pathway linked to CD146 engagement in human endothelial cells". J. Biol. Chem. 276 (2): 1564–9. doi:10.1074/jbc.M007065200. PMID 11036077.
↑ Astier A, Avraham H, Manie SN, Groopman J, Canty T, Avraham S, Freedman AS (January 1997). "The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to p130cas". J. Biol. Chem. 272 (1): 228–32. doi:10.1074/jbc.272.1.228. PMID 8995252.
1 2 Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I (May 2004). "Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites". J. Cell. Sci. 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. PMID 15128873.
↑ Sanjay A, Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne WC, Baron R (January 2001). "Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility". J. Cell Biol. 152 (1): 181–95. doi:10.1083/jcb.152.1.181. PMC 2193648. PMID 11149930.
↑ Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J (March 1999). "Identification of a new Pyk2 target protein with Arf-GAP activity". Mol. Cell. Biol. 19 (3): 2338–50. PMC 84026. PMID 10022920.
1 2 3 Seabold GK, Burette A, Lim IA, Weinberg RJ, Hell JW (April 2003). "Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102". J. Biol. Chem. 278 (17): 15040–8. doi:10.1074/jbc.M212825200. PMID 12576483.
↑ Felsch JS, Lane WS, Peralta EG (May 1999). "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol. 9 (9): 485–8. doi:10.1016/s0960-9822(99)80214-0. PMID 10322114.
↑ Ganju RK, Hatch WC, Avraham H, Ona MA, Druker B, Avraham S, Groopman JE (March 1997). "RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes". J. Exp. Med. 185 (6): 1055–63. doi:10.1084/jem.185.6.1055. PMC 2196239. PMID 9091579.
↑ Katagiri T, Takahashi T, Sasaki T, Nakamura S, Hattori S (June 2000). "Protein-tyrosine kinase Pyk2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402". J. Biol. Chem. 275 (26): 19645–52. doi:10.1074/jbc.M909828199. PMID 10867021.
↑ Qian D, Lev S, van Oers NS, Dikic I, Schlessinger J, Weiss A (April 1997). "Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling". J. Exp. Med. 185 (7): 1253–9. doi:10.1084/jem.185.7.1253. PMC 2196260. PMID 9104812.
↑ Liu Y, Zhang G, Gao C, Hou X (August 2001). "NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion". Brain Res. 909 (1-2): 51–8. doi:10.1016/s0006-8993(01)02619-1. PMID 11478920.
↑ Wang Q, Xie Y, Du QS, Wu XJ, Feng X, Mei L, McDonald JM, Xiong WC (February 2003). "Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin". J. Cell Biol. 160 (4): 565–75. doi:10.1083/jcb.200207036. PMC 2173747. PMID 12578912.
↑ Benzing T, Gerke P, Höpker K, Hildebrandt F, Kim E, Walz G (August 2001). "Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2". Proc. Natl. Acad. Sci. U.S.A. 98 (17): 9784–9. doi:10.1073/pnas.171269898. PMC 55530. PMID 11493697.
↑ Lev S, Hernandez J, Martinez R, Chen A, Plowman G, Schlessinger J (March 1999). "Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein". Mol. Cell. Biol. 19 (3): 2278–88. doi:10.1128/mcb.19.3.2278. PMC 84020. PMID 10022914.
↑ Chauhan D, Pandey P, Hideshima T, Treon S, Raje N, Davies FE, Shima Y, Tai YT, Rosen S, Avraham S, Kharbanda S, Anderson KC (September 2000). "SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells". J. Biol. Chem. 275 (36): 27845–50. doi:10.1074/jbc.M003428200. PMID 10880513.
↑ Ganju RK, Brubaker SA, Chernock RD, Avraham S, Groopman JE (June 2000). "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". J. Biol. Chem. 275 (23): 17263–8. doi:10.1074/jbc.M000689200. PMID 10747947.
1 2 Kumar S, Avraham S, Bharti A, Goyal J, Pandey P, Kharbanda S (October 1999). "Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase SHPTP1". J. Biol. Chem. 274 (43): 30657–63. doi:10.1074/jbc.274.43.30657. PMID 10521452.
1 2 Matsuya M, Sasaki H, Aoto H, Mitaka T, Nagura K, Ohba T, Ishino M, Takahashi S, Suzuki R, Sasaki T (January 1998). "Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions". J. Biol. Chem. 273 (2): 1003–14. doi:10.1074/jbc.273.2.1003. PMID 9422762.
↑ Hiregowdara D, Avraham H, Fu Y, London R, Avraham S (April 1997). "Tyrosine phosphorylation of the related adhesion focal tyrosine kinase in megakaryocytes upon stem cell factor and phorbol myristate acetate stimulation and its association with paxillin". J. Biol. Chem. 272 (16): 10804–10. doi:10.1074/jbc.272.16.10804. PMID 9099734.
↑ Chow A, Davis AJ, Gawler DJ (March 2000). "Identification of a novel protein complex containing annexin VI, Fyn, Pyk2, and the p120(GAP) C2 domain". FEBS Lett. 469 (1): 88–92. doi:10.1016/s0014-5793(00)01252-7. PMID 10708762.
↑ Zrihan-Licht S, Fu Y, Settleman J, Schinkmann K, Shaw L, Keydar I, Avraham S, Avraham H (March 2000). "RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion". Oncogene 19 (10): 1318–28. doi:10.1038/sj.onc.1203422. PMID 10713673.
↑ Ueda H, Abbi S, Zheng C, Guan JL (April 2000). "Suppression of Pyk2 kinase and cellular activities by FIP200". J. Cell Biol. 149 (2): 423–30. doi:10.1083/jcb.149.2.423. PMC 2175150. PMID 10769033.
↑ Keely SJ, Calandrella SO, Barrett KE (April 2000). "Carbachol-stimulated transactivation of epidermal growth factor receptor and mitogen-activated protein kinase in T(84) cells is mediated by intracellular Ca2+, PYK-2, and p60(src)". J. Biol. Chem. 275 (17): 12619–25. doi:10.1074/jbc.275.17.12619. PMID 10777553.
↑ Dikic I, Tokiwa G, Lev S, Courtneidge SA, Schlessinger J (October 1996). "A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation". Nature 383 (6600): 547–50. doi:10.1038/383547a0. PMID 8849729.
↑ Wang X, Yang Y, Guo X, Sampson ER, Hsu CL, Tsai MY, Yeh S, Wu G, Guo Y, Chang C (May 2002). "Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator". J. Biol. Chem. 277 (18): 15426–31. doi:10.1074/jbc.M111218200. PMID 11856738.
↑ Thomas SM, Hagel M, Turner CE (January 1999). "Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin". J. Cell. Sci. 112 (2): 181–90. PMID 9858471.

PTK2B

Function

Interactions

See also

References

Further reading