PTK2B explained

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.

The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration ^[3], nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. In addition, SOCE-induced Pyk2 activation mediates disassembly of endothelial adherens junctions, via tyrosine (Y1981-residue) phosphorylation of VE-PTP.^[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.

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.^[4]

Interactions

PTK2B has been shown to interact with:

• BCAR1,^{[5] [6] [7]}
• Cbl gene,^{[8] [9]}
• DDEF2,^[10]
• DLG3,
• DLG4,
• Ewing sarcoma breakpoint region 1,^[11]
• FYN,^{[12] [13] [14]}
• GRIN2A,^{[15] [16]}
• Gelsolin,^[17]
• NPHP1,^[18]
• PITPNM1,^[19]
• PTPN11,^[20]
• PTPN6,^{[21] [22]}
• Paxillin,^{[6] [23]}
• RAS p21 protein activator 1,^{[24] [25]}
• RB1CC1,^[26]
• SORBS2,^[8]
• Src,^{[22] [27] [28]} and
• TGFB1I1,^{[29] [30] [31]}

• VE-PTP^[3]

See also

• Tyrosine kinase

Further reading

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

Notes and References

1. Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J . Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions . Nature . 376 . 6543 . 737–45 . September 1995 . 7544443 . 10.1038/376737a0 . 1995Natur.376..737L . 4320927 . free .
2. Avraham S, London R, Fu Y, Ota S, Hiregowdara D, Li J, Jiang S, Pasztor LM, White RA, Groopman JE . Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain . J. Biol. Chem. . 270 . 46 . 27742–51 . 1995 . 7499242 . 10.1074/jbc.270.46.27742 . free.
3. Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C . 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. Apr 2017 . 28385807 . 5495943 . 10.1152/ajplung.00008.2017 .
4. Web site: Entrez Gene: PTK2B PTK2B protein tyrosine kinase 2 beta.
5. 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 . 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 . February 1997 . 9020138 . 10.1074/jbc.272.7.4230. free . 20.500.12613/9177 . free .
6. Anfosso F, Bardin N, Vivier E, Sabatier F, Sampol J, Dignat-George F . Outside-in signaling pathway linked to CD146 engagement in human endothelial cells . J. Biol. Chem. . 276 . 2 . 1564–9 . January 2001 . 11036077 . 10.1074/jbc.M007065200 . free .
7. Astier A, Avraham H, Manie SN, Groopman J, Canty T, Avraham S, Freedman AS . 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 . January 1997 . 8995252 . 10.1074/jbc.272.1.228. free .
8. Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I . 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 . May 2004 . 15128873 . 10.1242/jcs.01148 . 14083271 .
9. Sanjay A, Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne WC, Baron R . 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 . January 2001 . 11149930 . 2193648 . 10.1083/jcb.152.1.181.
10. Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J . Identification of a new Pyk2 target protein with Arf-GAP activity . Mol. Cell. Biol. . 19 . 3 . 2338–50 . March 1999 . 10022920 . 84026 . 10.1128/MCB.19.3.2338.
11. Felsch JS, Lane WS, Peralta EG . Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS . Curr. Biol. . 9 . 9 . 485–8 . May 1999 . 10322114 . 10.1016/s0960-9822(99)80214-0. 15389306 . free . 1999CBio....9..485F .
12. Ganju RK, Hatch WC, Avraham H, Ona MA, Druker B, Avraham S, Groopman JE . 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 . March 1997 . 9091579 . 2196239 . 10.1084/jem.185.6.1055.
13. Katagiri T, Takahashi T, Sasaki T, Nakamura S, Hattori S . 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 . June 2000 . 10867021 . 10.1074/jbc.M909828199 . free .
14. Qian D, Lev S, van Oers NS, Dikic I, Schlessinger J, Weiss A . Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling . J. Exp. Med. . 185 . 7 . 1253–9 . April 1997 . 9104812 . 2196260 . 10.1084/jem.185.7.1253.
15. Seabold GK, Burette A, Lim IA, Weinberg RJ, Hell JW . 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 . April 2003 . 12576483 . 10.1074/jbc.M212825200 . free .
16. Liu Y, Zhang G, Gao C, Hou X . 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 . August 2001 . 11478920 . 10.1016/s0006-8993(01)02619-1. 21062909 .
17. Wang Q, Xie Y, Du QS, Wu XJ, Feng X, Mei L, McDonald JM, Xiong WC . Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin . J. Cell Biol. . 160 . 4 . 565–75 . February 2003 . 12578912 . 2173747 . 10.1083/jcb.200207036 .
18. Benzing T, Gerke P, Höpker K, Hildebrandt F, Kim E, Walz G . Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2 . Proc. Natl. Acad. Sci. U.S.A. . 98 . 17 . 9784–9 . August 2001 . 11493697 . 55530 . 10.1073/pnas.171269898 . 2001PNAS...98.9784B . free .
19. Lev S, Hernandez J, Martinez R, Chen A, Plowman G, Schlessinger J . Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein . Mol. Cell. Biol. . 19 . 3 . 2278–88 . March 1999 . 10022914 . 84020 . 10.1128/mcb.19.3.2278.
20. Chauhan D, Pandey P, Hideshima T, Treon S, Raje N, Davies FE, Shima Y, Tai YT, Rosen S, Avraham S, Kharbanda S, Anderson KC . SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells . J. Biol. Chem. . 275 . 36 . 27845–50 . September 2000 . 10880513 . 10.1074/jbc.M003428200 . free .
21. Ganju RK, Brubaker SA, Chernock RD, Avraham S, Groopman JE . Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk . J. Biol. Chem. . 275 . 23 . 17263–8 . June 2000 . 10747947 . 10.1074/jbc.M000689200 . free .
22. Kumar S, Avraham S, Bharti A, Goyal J, Pandey P, Kharbanda S . Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase SHPTP1 . J. Biol. Chem. . 274 . 43 . 30657–63 . October 1999 . 10521452 . 10.1074/jbc.274.43.30657. free .
23. Hiregowdara D, Avraham H, Fu Y, London R, Avraham S . 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 . April 1997 . 9099734 . 10.1074/jbc.272.16.10804. free .
24. Chow A, Davis AJ, Gawler DJ . Identification of a novel protein complex containing annexin VI, Fyn, Pyk2, and the p120(GAP) C2 domain . FEBS Lett. . 469 . 1 . 88–92 . March 2000 . 10708762 . 10.1016/s0014-5793(00)01252-7. 21394463 . free .
25. Zrihan-Licht S, Fu Y, Settleman J, Schinkmann K, Shaw L, Keydar I, Avraham S, Avraham H . 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 . March 2000 . 10713673 . 10.1038/sj.onc.1203422 . free .
26. Ueda H, Abbi S, Zheng C, Guan JL . Suppression of Pyk2 kinase and cellular activities by FIP200 . J. Cell Biol. . 149 . 2 . 423–30 . April 2000 . 10769033 . 2175150 . 10.1083/jcb.149.2.423.
27. Keely SJ, Calandrella SO, Barrett KE . 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 . April 2000 . 10777553 . 10.1074/jbc.275.17.12619. free .
28. Dikic I, Tokiwa G, Lev S, Courtneidge SA, Schlessinger J . A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation . Nature . 383 . 6600 . 547–50 . October 1996 . 8849729 . 10.1038/383547a0 . 1996Natur.383..547D . 4328514 .
29. Matsuya M, Sasaki H, Aoto H, Mitaka T, Nagura K, Ohba T, Ishino M, Takahashi S, Suzuki R, Sasaki T . 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 . January 1998 . 9422762 . 10.1074/jbc.273.2.1003. free .
30. Wang X, Yang Y, Guo X, Sampson ER, Hsu CL, Tsai MY, Yeh S, Wu G, Guo Y, Chang C . Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator . J. Biol. Chem. . 277 . 18 . 15426–31 . May 2002 . 11856738 . 10.1074/jbc.M111218200 . free .
31. Thomas SM, Hagel M, Turner CE . Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin . J. Cell Sci. . 112 . 2. 181–90 . January 1999 . 10.1242/jcs.112.2.181 . 9858471 .