PTK2B

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 66,390,706 bp [2] End 66,518,501 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 10 monocyte spleen Brodmann area 9 bone marrow cells lymph node frontal pole blood appendix skin of abdomen Top expressed in superior frontal gyrus olfactory tubercle piriform cortex entorhinal cortex hippocampus proper subiculum nucleus accumbens prefrontal cortex amygdala cingulate gyrus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-containing complex binding kinase activity signaling receptor binding ATP binding protein kinase activity non-membrane spanning protein tyrosine kinase activity transferase activity 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 nucleus cell projection membrane raft lamellipodium apical dendrite growth cone plasma membrane axon neuronal cell body cell cortex cell body 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 depression positive regulation of excitatory postsynaptic potential regulation of cGMP-mediated signaling response to ethanol neuron projection development negative regulation of cell population proliferation response to cocaine apoptotic process regulation of actin cytoskeleton reorganization positive regulation of 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 protein autophosphorylation innate immune response 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 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 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 population proliferation regulation of calcium-mediated signaling positive regulation of cell population proliferation positive regulation of neuron projection development glial cell proliferation activation of Janus kinase activity peptidyl-tyrosine phosphorylation regulation of ubiquitin-dependent protein catabolic process signal transduction long-term potentiation cell adhesion interleukin-7-mediated signaling pathway interleukin-2-mediated signaling pathway regulation of synaptic plasticity protein-containing 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: 66.39 – 66.52 Mb PubMed search [3] [4]
Wikidata
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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:

• 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. 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. "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 . hdl: 20.500.12613/9177 . 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. 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. 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. 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. 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

• 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 .