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Protein tyrosine kinase 2 beta
Protein PTK2B PDB 2FO6.png
Rendering based on PDB 2FO6.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM601212 MGI104908 HomoloGene23001 ChEMBL: 5469 GeneCards: PTK2B Gene
EC number
RNA expression pattern
PBB GE PTK2B 203110 at tn.png
More reference expression data
Species Human Mouse
Entrez 2185 19229
Ensembl ENSG00000120899 ENSMUSG00000059456
UniProt Q14289 Q9QVP9
RefSeq (mRNA) NM_004103 NM_001162365
RefSeq (protein) NP_004094 NP_001155837
Location (UCSC) Chr 8:
27.17 – 27.32 Mb
Chr 14:
66.15 – 66.28 Mb
PubMed search [1] [2]

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


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, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. This protein has been shown to bind CRK-associated substrate, nephrocystin, 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.[3]


PTK2B has been shown to interact with PTPN11,[4] PTPN6,[5][6] PITPNM1,[7] Gelsolin,[8] Src,[6][9][10] GRIN2A,[11][12] Ewing sarcoma breakpoint region 1,[13] RB1CC1,[14] TGFB1I1,[15][16][17] NPHP1,[18] BCAR1,[19][20][21] FYN,[22][23][24] DLG4,[11] DLG3,[11] DDEF2,[25] Cbl gene,[26][27] RAS p21 protein activator 1,[28][29] Paxillin[15][20][30] and SORBS2.[26]

See also[edit]


  1. ^ 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. 
  2. ^ Avraham S, London R, Fu Y, Ota S, Hiregowdara D, Li J, Jiang S, Pasztor LM, White RA, Groopman JE, et al. (January 1996). "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. 
  3. ^ "Entrez Gene: PTK2B PTK2B protein tyrosine kinase 2 beta". 
  4. ^ Chauhan, D; Pandey P, Hideshima T, Treon S, Raje N, Davies F E, Shima Y, Tai Y T, Rosen S, Avraham S, Kharbanda S, Anderson K C (September 2000). "SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells". J. Biol. Chem. (UNITED STATES) 275 (36): 27845–50. doi:10.1074/jbc.M003428200. ISSN 0021-9258. PMID 10880513. 
  5. ^ Ganju, R K; Brubaker S A; Chernock R D; Avraham S; Groopman J E (June 2000). "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". J. Biol. Chem. (UNITED STATES) 275 (23): 17263–8. doi:10.1074/jbc.M000689200. ISSN 0021-9258. PMID 10747947. 
  6. ^ a b 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. (UNITED STATES) 274 (43): 30657–63. doi:10.1074/jbc.274.43.30657. ISSN 0021-9258. PMID 10521452. 
  7. ^ 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. (UNITED STATES) 19 (3): 2278–88. ISSN 0270-7306. PMC 84020. PMID 10022914. 
  8. ^ Wang, Qiang; Xie Yi; Du Quan-Sheng; Wu Xiao-Jun; Feng Xu; Mei Lin; McDonald Jay M; Xiong Wen-Cheng (February 2003). "Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin". J. Cell Biol. (United States) 160 (4): 565–75. doi:10.1083/jcb.200207036. ISSN 0021-9525. PMC 2173747. PMID 12578912. 
  9. ^ Keely, S J; Calandrella S O; Barrett K E (April 2000). "Carbachol-stimulated transactivation of epidermal growth factor receptor and mitogen-activated protein kinase in T(84) cells is mediated by intracellular ca(2+), PYK-2, and p60(src)". J. Biol. Chem. (UNITED STATES) 275 (17): 12619–25. doi:10.1074/jbc.275.17.12619. ISSN 0021-9258. PMID 10777553. 
  10. ^ Dikic, I; Tokiwa G; Lev S; Courtneidge S A; Schlessinger J (October 1996). "A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation". Nature (ENGLAND) 383 (6600): 547–50. doi:10.1038/383547a0. ISSN 0028-0836. PMID 8849729. 
  11. ^ a b c Seabold, Gail K; Burette Alain; Lim Indra A; Weinberg Richard J; Hell Johannes W (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. (United States) 278 (17): 15040–8. doi:10.1074/jbc.M212825200. ISSN 0021-9258. PMID 12576483. 
  12. ^ 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. (Netherlands) 909 (1–2): 51–8. doi:10.1016/S0006-8993(01)02619-1. ISSN 0006-8993. PMID 11478920. 
  13. ^ Felsch, J S; Lane W S; Peralta E G (May 1999). "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol. (ENGLAND) 9 (9): 485–8. doi:10.1016/S0960-9822(99)80214-0. ISSN 0960-9822. PMID 10322114. 
  14. ^ Ueda, H; Abbi S; Zheng C; Guan J L (April 2000). "Suppression of Pyk2 kinase and cellular activities by FIP200". J. Cell Biol. (UNITED STATES) 149 (2): 423–30. doi:10.1083/jcb.149.2.423. ISSN 0021-9525. PMC 2175150. PMID 10769033. 
  15. ^ a b 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. (UNITED STATES) 273 (2): 1003–14. doi:10.1074/jbc.273.2.1003. ISSN 0021-9258. PMID 9422762. 
  16. ^ Wang, Xin; Yang Yue; Guo Xiaojian; Sampson Erik R; Hsu Cheng-Lung; Tsai Meng-Yin; Yeh Shuyuan; Wu Guan; Guo Yinglu; Chang Chawnshang (May 2002). "Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator". J. Biol. Chem. (United States) 277 (18): 15426–31. doi:10.1074/jbc.M111218200. ISSN 0021-9258. PMID 11856738. 
  17. ^ Thomas, S M; Hagel M; Turner C E (January 1999). "Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin". J. Cell. Sci. (ENGLAND) 112 (2): 181–90. ISSN 0021-9533. PMID 9858471. 
  18. ^ 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. (United States) 98 (17): 9784–9. doi:10.1073/pnas.171269898. ISSN 0027-8424. PMC 55530. PMID 11493697. 
  19. ^ Manié, S N; Beck A R, Astier A, Law S F, Canty T, Hirai H, Druker B J, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin J D, Golemis E A, Freedman A S (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. (UNITED STATES) 272 (7): 4230–6. doi:10.1074/jbc.272.7.4230. ISSN 0021-9258. PMID 9020138. 
  20. ^ a b 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. (United States) 276 (2): 1564–9. doi:10.1074/jbc.M007065200. ISSN 0021-9258. PMID 11036077. 
  21. ^ Astier, A; Avraham H; Manie S N; Groopman J; Canty T; Avraham S; Freedman A S (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. (UNITED STATES) 272 (1): 228–32. doi:10.1074/jbc.272.1.228. ISSN 0021-9258. PMID 8995252. 
  22. ^ Ganju, R K; Hatch W C; Avraham H; Ona M A; Druker B; Avraham S; Groopman J E (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. (UNITED STATES) 185 (6): 1055–63. doi:10.1084/jem.185.6.1055. ISSN 0022-1007. PMC 2196239. PMID 9091579. 
  23. ^ 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. (UNITED STATES) 275 (26): 19645–52. doi:10.1074/jbc.M909828199. ISSN 0021-9258. PMID 10867021. 
  24. ^ Qian, D; Lev S; van Oers N S; Dikic I; Schlessinger J; Weiss A (April 1997). "Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling". J. Exp. Med. (UNITED STATES) 185 (7): 1253–9. doi:10.1084/jem.185.7.1253. ISSN 0022-1007. PMC 2196260. PMID 9104812. 
  25. ^ Andreev, J; Simon J P; Sabatini D D; Kam J; Plowman G; Randazzo P A; Schlessinger J (March 1999). "Identification of a new Pyk2 target protein with Arf-GAP activity". Mol. Cell. Biol. (UNITED STATES) 19 (3): 2338–50. ISSN 0270-7306. PMC 84026. PMID 10022920. 
  26. ^ a b Haglund, Kaisa; Ivankovic-Dikic Inga, Shimokawa Noriaki, Kruh Gary D, Dikic Ivan (May 2004). "Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites". J. Cell. Sci. (England) 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. ISSN 0021-9533. PMID 15128873. 
  27. ^ Sanjay, A; Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne W C, 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. (United States) 152 (1): 181–95. doi:10.1083/jcb.152.1.181. ISSN 0021-9525. PMC 2193648. PMID 11149930. 
  28. ^ Chow, A; Davis A J; Gawler D J (March 2000). "Identification of a novel protein complex containing annexin VI, Fyn, Pyk2, and the p120(GAP) C2 domain". FEBS Lett. (NETHERLANDS) 469 (1): 88–92. doi:10.1016/S0014-5793(00)01252-7. ISSN 0014-5793. PMID 10708762. 
  29. ^ 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 (ENGLAND) 19 (10): 1318–28. doi:10.1038/sj.onc.1203422. ISSN 0950-9232. PMID 10713673. 
  30. ^ 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. (UNITED STATES) 272 (16): 10804–10. doi:10.1074/jbc.272.16.10804. ISSN 0021-9258. PMID 9099734. 

Further reading[edit]

  • Avraham S, Avraham H (1998). "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.