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.
^Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM et al. (September 1995). "Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions". Nature376 (6543): 737–45. doi:10.1038/376737a0. PMID7544443.
^Avraham S, London R, Fu Y, Ota S, Hiregowdara D, Li J 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. PMID7499242.Check date values in: |year= / |date= mismatch (help)
^Manié SN, Beck AR, Astier A, Law SF, Canty T, Hirai H et al. (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. PMID9020138.
^ abAnfosso 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. PMID11036077.
^Astier A, Avraham H, Manie SN, Groopman J, Canty T, Avraham S et al. (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. PMID8995252.
^ abHaglund 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. PMID15128873.
^ abcSeabold 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. PMID12576483.
^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. PMID10322114.
^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. PMID10867021.
^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. PMID11478920.
^Chauhan D, Pandey P, Hideshima T, Treon S, Raje N, Davies FE et al. (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. PMID10880513.
^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. PMID10747947.
^ abKumar 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. PMID10521452.
^ abMatsuya M, Sasaki H, Aoto H, Mitaka T, Nagura K, Ohba T et al. (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. PMID9422762.
^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. PMID9099734.
^Zrihan-Licht S, Fu Y, Settleman J, Schinkmann K, Shaw L, Keydar I et al. (March 2000). "RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion". Oncogene19 (10): 1318–28. doi:10.1038/sj.onc.1203422. PMID10713673.
^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. PMID10777553.
^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". Nature383 (6600): 547–50. doi:10.1038/383547a0. PMID8849729.
^Wang X, Yang Y, Guo X, Sampson ER, Hsu CL, Tsai MY et al. (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. PMID11856738.
^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. PMID9858471.