Tyr402

Site Information
CSIESDIyAEIPDET SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447955

In vivo Characterization
Methods used to characterize site in vivo:	immunoprecipitation ( 7 , 8 , 17 ) , mass spectrometry ( 9 , 16 ) , mutation of modification site ( 4 , 5 , 17 , 18 , 21 , 24 , 25 , 30 ) , phospho-antibody ( 1 , 2 , 3 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ) , western blotting ( 1 , 2 , 3 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 22 , 23 , 24 , 27 )
Disease tissue studied:	lymphoma ( 12 ) , T cell lymphoma ( 12 ) , melanoma skin cancer ( 1 , 10 ) , Wiskott-Aldrich syndrome ( 19 )
Relevant cell line - cell type - tissue:	'brain, hippocampus' ( 2 ) , 'neuron, cortical'-brain ( 27 ) , 293 (epithelial) ( 17 , 24 , 25 , 27 , 30 ) , 3T3 (fibroblast) [Pyk2 (human), transfection, stable Pyk2 (v5-His tagged) transfection, in RU-486 (mifepristone)-inducible expression system] ( 16 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 23 ) , 3T3 (fibroblast) ( 16 ) , AB.1 (T lymphocyte) ( 13 ) , B16 (melanocyte) ( 1 , 10 ) , BW5147 (T lymphocyte) ( 12 ) , embryo ( 14 ) , endothelial ( 15 ) , EpH4 (epithelial) ( 6 ) , GT1-7 (neuron) ( 26 ) , H9c2 (myoblast) ( 7 ) , heart ( 7 ) , HEK293T (epithelial) ( 28 ) , HLMVECs ( 8 ) , lung ( 8 ) , macrophage-bone marrow ( 3 ) , MEF (fibroblast) ( 2 , 14 ) , myeloid-bone marrow [WASP (mouse)] ( 19 ) , neuron-'brain, hippocampus' ( 4 ) , neuron:synaptosome ( 2 ) , NMuMG (epithelial) ( 29 ) , osteoblast [JNK1 (human)] ( 18 ) , osteoblast [MEK1 (human)] ( 18 ) , osteoclast ( 21 , 25 ) , osteoclast-like cell ( 17 , 22 , 30 ) , PC-12 (chromaffin) ( 20 ) , prostate ( 11 ) , RAW 264.7 (macrophage) ( 9 )

Upstream Regulation
Regulatory protein:	BVR (human) ( 2 ) , CD45 (mouse) ( 12 ) , DYN1 (mouse) ( 17 ) , FAK (mouse) ( 15 ) , FAK iso2 (mouse) ( 14 ) , JNK1 (human) ( 18 ) , KRas (mouse) ( 11 ) , LPL (human) ( 3 ) , Plectin-1 (human) ( 1 ) , PTPRE (mouse) ( 22 ) , Pyk2 (mouse) ( 16 ) , RHOC (mouse) ( 10 ) , Src iso1 (mouse) ( 10 )
Putative in vivo kinases:	Pyk2 (mouse) ( 4 , 5 , 16 , 22 , 25 ) , Src (human) ( 1 ) , Src iso1 (mouse) ( 12 , 17 )
Kinases, in vitro:	Pyk2 (mouse) ( 25 )
Treatments:	1-butanol ( 20 ) , AG1478 ( 26 ) , antibody ( 13 ) , ATP ( 3 ) , BAPTA-AM ( 18 , 26 ) , calmidazolium ( 27 ) , CPCCOEt ( 27 ) , dexamethasone ( 18 ) , DHPG ( 27 ) , EGF ( 20 ) , EGTA ( 12 , 18 ) , endothelin ( 23 ) , gadolinium ( 18 ) , GF109203X ( 27 ) , GnRH ( 26 ) , Go_6983 ( 26 ) , GSK2256098 ( 6 ) , H2O2 ( 7 , 13 , 20 ) , ionomycin ( 13 ) , ischemia/reperfusion ( 7 ) , latrunculin_A ( 12 ) , low_cell_density ( 29 ) , LPS ( 3 ) , LY294002 ( 12 ) , MK801 ( 27 ) , MPEP ( 27 ) , nigericin ( 3 ) , ophiobolin ( 27 ) , PD98059 ( 18 ) , PF-431396 ( 3 , 6 , 7 ) , PF-4594755 ( 16 ) , phorbol_ester ( 2 , 26 , 27 ) , PKCI_19-27 ( 27 ) , PP1 ( 18 ) , PP2 ( 12 , 13 , 17 , 20 ) , PP3 ( 13 ) , pyrintegrin ( 2 ) , RGD ( 19 ) , Ro31-8220 ( 26 ) , SB203580 ( 18 ) , SP600125 ( 18 ) , SU6656 ( 17 ) , t-butanol ( 20 ) , taxol ( 12 ) , TGF-beta ( 29 ) , thapsigargin ( 13 ) , thrombin ( 8 ) , TNF ( 19 , 23 ) , U73122 ( 12 ) , U73343 ( 12 ) , vanadate ( 17 ) , W-7 ( 27 ) , wortmannin ( 18 )

Downstream Regulation
Effects of modification on Pyk2:	enzymatic activity, induced ( 18 ) , molecular association, regulation ( 17 , 21 , 25 , 30 ) , phosphorylation ( 17 )
Effects of modification on biological processes:	apoptosis, induced ( 18 ) , carcinogenesis, induced ( 1 ) , cell adhesion, altered ( 19 ) , cell adhesion, induced ( 1 , 2 ) , cell growth, induced ( 1 ) , cytoskeletal reorganization ( 21 , 25 ) , neural plasticity ( 2 ) , transcription, altered ( 4 )
Induce interaction with:	DYN1 (human) ( 17 ) , Src (human) ( 30 ) , Src iso1 (mouse) ( 21 , 25 )

References
1	Mizuta K, et al. (2022) Plectin promotes tumor formation by B16 mouse melanoma cells via regulation of Rous sarcoma oncogene activity. BMC Cancer 22, 936 36038818 Curated Info
2	Vasavda C, et al. (2022) Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling. Sci Signal 15, eabh3066 35536885 Curated Info
3	Joshi H, et al. (2022) L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis. Cell Rep 38, 110507 35294888 Curated Info
4	Zheng J, et al. (2021) Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner. J Mol Cell Biol 13 34529077 Curated Info
5	Cong Y, et al. (2020) Ptk2b deletion improves mice folliculogenesis and fecundity via inhibiting follicle loss mediated by Erk pathway. J Cell Physiol 236 32608523 Curated Info
6	Nakatsu D, Kano F, Shinozaki-Narikawa N, Murata M (2019) Pyk2-dependent phosphorylation of LSR enhances localization of LSR and tricellulin at tricellular tight junctions. PLoS One 14, e0223300 31574128 Curated Info
7	Bibli SI, et al. (2017) Tyrosine phosphorylation of eNOS regulates myocardial survival after an ischaemic insult: role of PYK2. Cardiovasc Res 113, 926-937 28444132 Curated Info
8	Soni D, et al. (2017) Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca(2+) entry regulates disassembly of adherens junctions. Am J Physiol Lung Cell Mol Physiol 312, L1003-L1017 28385807 Curated Info
9	Pinto SM, et al. (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15, 532-44 25367039 Curated Info
10	Arpaia E, et al. (2012) The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk. Oncogene 31, 884-96 21765460 Curated Info
11	Drake JM, et al. (2012) Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression. Proc Natl Acad Sci U S A 109, 1643-8 22307624 Curated Info
12	Wong NK, Lai JC, Maeshima N, Johnson P (2011) CD44-mediated elongated T cell spreading requires Pyk2 activation by Src family kinases, extracellular calcium, phospholipase C and phosphatidylinositol-3 kinase. Cell Signal 23, 812-9 21238585 Curated Info
13	Lysechko TL, Cheung SM, Ostergaard HL (2010) Regulation of the tyrosine kinase Pyk2 by calcium is through production of reactive oxygen species in cytotoxic T lymphocytes. J Biol Chem 285, 31174-84 20688918 Curated Info
14	Lim ST, et al. (2010) Knock-in mutation reveals an essential role for focal adhesion kinase activity in blood vessel morphogenesis and cell motility-polarity but not cell proliferation. J Biol Chem 285, 21526-36 20442405 Curated Info
15	Zhao X, et al. (2010) Role of kinase-independent and -dependent functions of FAK in endothelial cell survival and barrier function during embryonic development. J Cell Biol 189, 955-65 20530207 Curated Info
16	Bonnette PC, et al. (2010) Phosphoproteomic characterization of PYK2 signaling pathways involved in osteogenesis. J Proteomics 73, 1306-20 20116462 Curated Info
17	Bruzzaniti A, et al. (2009) Dynamin reduces Pyk2 Y402 phosphorylation and SRC binding in osteoclasts. Mol Cell Biol 29, 3644-56 19380485 Curated Info
18	Plotkin LI, Manolagas SC, Bellido T (2007) Glucocorticoids induce osteocyte apoptosis by blocking focal adhesion kinase-mediated survival. Evidence for inside-out signaling leading to anoikis. J Biol Chem 282, 24120-30 17581824 Curated Info
19	Zhang H, et al. (2006) Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils. Immunity 25, 285-95 16901726 Curated Info
20	Banno Y, et al. (2005) Implication of phospholipase D2 in oxidant-induced phosphoinositide 3-kinase signaling via Pyk2 activation in PC12 cells. J Biol Chem 280, 16319-24 15705590 Curated Info
21	Miyazaki T, et al. (2004) Src kinase activity is essential for osteoclast function. J Biol Chem 279, 17660-6 14739300 Curated Info
22	Chiusaroli R, et al. (2004) Tyrosine phosphatase epsilon is a positive regulator of osteoclast function in vitro and in vivo. Mol Biol Cell 15, 234-44 14528021 Curated Info
23	Rachdaoui N, Nagy LE (2003) Endothelin-1-stimulated glucose uptake is desensitized by tumor necrosis factor-alpha in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 285, E545-51 12773307 Curated Info
24	Kruljac-Letunic A, et al. (2003) The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. J Biol Chem 278, 29560-70 12771146 Curated Info
25	Lakkakorpi PT, et al. (2003) PYK2 autophosphorylation, but not kinase activity, is necessary for adhesion-induced association with c-Src, osteoclast spreading, and bone resorption. J Biol Chem 278, 11502-12 12514172 Curated Info
26	Shah BH, Soh JW, Catt KJ (2003) Dependence of gonadotropin-releasing hormone-induced neuronal MAPK signaling on epidermal growth factor receptor transactivation. J Biol Chem 278, 2866-75 12446705 Curated Info
27	Heidinger V, et al. (2002) Metabotropic glutamate receptor 1-induced upregulation of NMDA receptor current: mediation through the Pyk2/Src-family kinase pathway in cortical neurons. J Neurosci 22, 5452-61 12097497 Curated Info
28	Benzing T, et al. (2001) Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2. Proc Natl Acad Sci U S A 98, 9784-9 11493697 Curated Info
29	Nakamura K, Yano H, Schaefer E, Sabe H (2001) Different modes and qualities of tyrosine phosphorylation of Fak and Pyk2 during epithelial-mesenchymal transdifferentiation and cell migration: analysis of specific phosphorylation events using site-directed antibodies. Oncogene 20, 2626-35 11420674 Curated Info
30	Sanjay A, et al. (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, 181-95 11149930 Curated Info