PTK2B

Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.[5][6]

PTK2B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LK4, 3CC6, 3ET7, 3FZO, 3FZP, 3FZR, 3FZS, 3FZT, 3GM1, 3GM2, 3GM3, 3H3C, 3U3F, 4EKU, 4H1J, 4H1M, 4R32, 4XEK, 4XEF, 4XEV
Identifiers
Aliases	PTK2B, CADTK, CAKB, FADK2, FAK2, PKB, PTK, PYK2, RAFTK, protein tyrosine kinase 2 beta
External IDs	OMIM: 601212 MGI: 104908 HomoloGene: 23001 GeneCards: PTK2B
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8p21.2 Start 27,311,482 bp[1] End 27,459,391 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 D1|14 34.36 cM Start 66,153,257 bp[2] End 66,281,052 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0032403 macromolecular complex binding • kinase activity • receptor binding • ATP binding • protein kinase activity • non-membrane spanning protein tyrosine kinase activity • transferase activity • GO:0001948 protein binding • nucleotide binding • 3-phosphoinositide-dependent protein kinase binding • NMDA glutamate receptor activity • signal transducer activity • calmodulin-dependent protein kinase activity • enzyme binding • protein tyrosine kinase activity • ubiquitin protein ligase binding • protein C-terminus binding Cellular component • membrane • focal adhesion • extrinsic component of cytoplasmic side of plasma membrane • NMDA selective glutamate receptor complex • perinuclear region of cytoplasm • cytoskeleton • cell nucleus • cell projection • membrane raft • lamellipodium • apical dendrite • growth cone • cell membrane • axon • neuronal cell body • cell cortex • cell body • GO:0097483, GO:0097481 postsynaptic density • cell junction • dendrite • cytosol • cytoplasm • dendritic spine • postsynapse • glutamatergic synapse Biological process • negative regulation of neuron apoptotic process • cellular response to retinoic acid • adaptive immune response • positive regulation of actin filament polymerization • tumor necrosis factor-mediated signaling pathway • positive regulation of JNK cascade • regulation of angiogenesis • marginal zone B cell differentiation • negative regulation of muscle cell apoptotic process • positive regulation of translation • stress fiber assembly • negative regulation of ossification • protein phosphorylation • cell surface receptor signaling pathway • vascular endothelial growth factor receptor signaling pathway • regulation of cell adhesion • positive regulation of reactive oxygen species metabolic process • angiogenesis • positive regulation of ERK1 and ERK2 cascade • long term synaptic depression • positive regulation of excitatory postsynaptic potential • regulation of cGMP-mediated signaling • response to ethanol • neuron projection development • negative regulation of cell proliferation • response to cocaine • apoptotic process • regulation of actin cytoskeleton reorganization • positive regulation of cellular protein metabolic process • epidermal growth factor receptor signaling pathway • actin filament organization • response to reactive oxygen species • chemokine-mediated signaling pathway • response to mechanical stimulus • signal complex assembly • bone resorption • response to lithium ion • response to osmotic stress • positive regulation of cell growth • positive regulation of nitric-oxide synthase activity • positive regulation of synaptic transmission, glutamatergic • ionotropic glutamate receptor signaling pathway • response to organonitrogen compound • positive regulation of DNA biosynthetic process • positive regulation of peptidyl-tyrosine phosphorylation • autophosphorylation • innate immune system • negative regulation of myeloid cell differentiation • response to immobilization stress • cell differentiation • phosphorylation • positive regulation of cell-matrix adhesion • positive regulation of JUN kinase activity • immune system process • regulation of release of sequestered calcium ion into cytosol • negative regulation of apoptotic process • sprouting angiogenesis • regulation of inositol trisphosphate biosynthetic process • response to glucose • cellular response to fluid shear stress • positive regulation of angiogenesis • response to calcium ion • regulation of NMDA receptor activity • cellular defense response • oocyte maturation • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • negative regulation of potassium ion transport • regulation of cell shape • peptidyl-tyrosine autophosphorylation • integrin-mediated signaling pathway • positive regulation of B cell chemotaxis • response to hormone • response to cAMP • regulation of nitric oxide biosynthetic process • regulation of establishment of cell polarity • response to hydrogen peroxide • regulation of macrophage chemotaxis • positive regulation of protein kinase activity • regulation of leukocyte chemotaxis • negative regulation of bone mineralization • regulation of cell migration • response to hypoxia • blood vessel endothelial cell migration • GO:0032861, GO:0032862, GO:0032856 activation of GTPase activity • positive regulation of cell migration • regulation of bone mineralization • positive regulation of cytosolic calcium ion concentration • positive regulation of nitric oxide biosynthetic process • response to stress • MAPK cascade • positive regulation of phosphatidylinositol 3-kinase activity • positive regulation of endothelial cell migration • focal adhesion assembly • regulation of cell proliferation • regulation of calcium-mediated signaling • positive regulation of cell proliferation • positive regulation of neuron projection development • glial cell proliferation • activation of Janus kinase activity • peptidyl-tyrosine phosphorylation • regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • response to drug • signal transduction • long-term synaptic potentiation • cell adhesion • interleukin-7-mediated signaling pathway • interleukin-2-mediated signaling pathway • regulation of synaptic plasticity • macromolecular complex assembly Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2185	19229
Ensembl	ENSG00000120899	ENSMUSG00000059456
UniProt	Q14289	Q9QVP9
RefSeq (mRNA)	NM_004103 NM_173174 NM_173175 NM_173176	NM_001162365 NM_001162366 NM_172498 NM_001360233
RefSeq (protein)	NP_004094 NP_775266 NP_775267 NP_775268	NP_001155837 NP_001155838 NP_766086 NP_001347162
Location (UCSC)	Chr 8: 27.31 – 27.46 Mb	Chr 14: 66.15 – 66.28 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[7]

The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration [8] , nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation.[7] In addition, SOCE-induced Pyk2 activation mediates disassembly of endothelial adherens junctions, via tyrosine (Y1981-residue) phosphorylation of VE-PTP.[8]

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.[7]

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.[7]

Interactions

PTK2B has been shown to interact with:

• BCAR1,[9][10][11]
• Cbl gene,[12][13]
• DDEF2,[14]
• DLG3,[15]
• DLG4,[15]
• Ewing sarcoma breakpoint region 1,[16]
• FYN,[17][18][19]
• GRIN2A,[15][20]
• Gelsolin,[21]
• NPHP1,[22]
• PITPNM1,[23]
• PTPN11,[24]
• PTPN6,[25][26]
• Paxillin,[10][27][28]
• RAS p21 protein activator 1,[29][30]
• RB1CC1,[31]
• SORBS2,[12]
• Src,[26][32][33] and
• TGFB1I1,[27][34][35]

• VE-PTP [8]

See also

• Tyrosine kinase

References

1. GRCh38: Ensembl release 89: ENSG00000120899 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000059456 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: PTK2B PTK2B protein tyrosine kinase 2 beta".
8. Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C (Apr 2017). "Pyk2 Phosphorylation of VE-PTP Downstream of STIM1 induced Ca2+ entry Regulates Disassembly of Adherens Junctions". American Journal of Physiology. Lung Cellular and Molecular Physiology. 312 (6): L1003–L1017. doi:10.1152/ajplung.00008.2017. PMC 5495943. PMID 28385807.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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. doi:10.1128/MCB.19.3.2338. PMC 84026. PMID 10022920.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.

Further reading

• Avraham S, Avraham H (1997). "Characterization of the novel focal adhesion kinase RAFTK in hematopoietic cells". Leuk. Lymphoma. 27 (3–4): 247–56. doi:10.3109/10428199709059681. PMID 9402324.
• Schlaepfer DD, Hauck CR, Sieg DJ (1999). "Signaling through focal adhesion kinase". Prog. Biophys. Mol. Biol. 71 (3–4): 435–78. doi:10.1016/S0079-6107(98)00052-2. PMID 10354709.
• Loeser RF (2002). "Integrins and cell signaling in chondrocytes". Biorheology. 39 (1–2): 119–24. PMID 12082274.

External links

• Overview of all the structural information available in the PDB for UniProt: Q14289 (Protein-tyrosine kinase 2-beta) at the PDBe-KB.