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PTK2B
Available structures
PDBOrtholog search: PDBe RCSB
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; OMA: PTK2B - orthologs
Orthologs
SpeciesHumanMouse
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: 66.39 – 66.52 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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:

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000120899 – Ensembl, May 2017
  2. ^ a b c 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. Bibcode: 1995Natur.376..737L. doi: 10.1038/376737a0. PMID  7544443. S2CID  4320927.
  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. ^ a b c d "Entrez Gene: PTK2B PTK2B protein tyrosine kinase 2 beta".
  8. ^ a b c 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. hdl: 20.500.12613/9177. PMID  9020138.
  10. ^ 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. 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. ^ a b 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. S2CID  14083271.
  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. ^ a b c 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. Bibcode: 1999CBio....9..485F. doi: 10.1016/s0960-9822(99)80214-0. PMID  10322114. S2CID  15389306.
  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. S2CID  21062909.
  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. Bibcode: 2001PNAS...98.9784B. 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. ^ 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. 274 (43): 30657–63. doi: 10.1074/jbc.274.43.30657. PMID  10521452.
  27. ^ 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. 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. S2CID  21394463.
  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. Bibcode: 1996Natur.383..547D. doi: 10.1038/383547a0. PMID  8849729. S2CID  4328514.
  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. doi: 10.1242/jcs.112.2.181. PMID  9858471.

Further reading

External links

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