Tyr402
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Home > Phosphorylation Site Page: > Tyr402  -  Pyk2 (mouse)

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

Upstream Regulation
Regulatory protein:
DYN1 (mouse) ( 12 ) , FAK (mouse) ( 10 ) , FAK iso2 (mouse) ( 9 ) , JNK1 (human) ( 13 ) , KRas (mouse) ( 6 ) , Pyk2 (mouse) ( 11 ) , RHOC (mouse) ( 5 ) , Src (mouse) ( 5 )
Putative in vivo kinases:
Pyk2 (mouse) ( 11 , 19 ) , Src (mouse) ( 12 )
Kinases, in vitro:
Pyk2 (mouse) ( 19 )
Treatments:
1-butanol ( 15 ) , AG1478 ( 20 ) , anti-CD3 ( 8 ) , BAPTA-AM ( 13 , 20 ) , calmidazolium ( 21 ) , CPCCOEt ( 21 ) , dexamethasone ( 13 ) , DHPG ( 21 ) , EGF ( 15 ) , EGTA ( 13 ) , endothelin ( 17 ) , gadolinium ( 13 ) , GF109203X ( 21 ) , GnRH ( 20 ) , Go_6983 ( 20 ) , H2O2 ( 2 , 8 , 15 ) , ionomycin ( 8 ) , ischemia/reperfusion ( 2 ) , low_cell_density ( 23 ) , MK801 ( 21 ) , MPEP ( 21 ) , ophiobolin ( 21 ) , PD98059 ( 13 ) , PF-431396 ( 2 ) , PF-4594755 ( 11 ) , phorbol_ester ( 20 , 21 ) , PKCI_19-27 ( 21 ) , PP1 ( 13 ) , PP2 ( 8 , 12 , 15 ) , PP3 ( 8 ) , RGD ( 14 ) , Ro31-8220 ( 20 ) , SB203580 ( 13 ) , SP600125 ( 13 ) , SU6656 ( 12 ) , t-butanol ( 15 ) , TGF-beta ( 23 ) , thapsigargin ( 8 ) , thrombin ( 3 ) , TNF ( 14 , 17 ) , vanadate ( 12 ) , W-7 ( 21 ) , wortmannin ( 13 )

Downstream Regulation
Effects of modification on Pyk2:
enzymatic activity, induced ( 13 ) , molecular association, regulation ( 12 , 16 , 19 , 24 ) , phosphorylation ( 12 )
Effects of modification on biological processes:
apoptosis, induced ( 13 ) , cell adhesion, altered ( 14 ) , cytoskeletal reorganization ( 16 , 19 )
Induce interaction with:
DYN1 (human) ( 12 ) , Src (human) ( 24 ) , Src (mouse) ( 16 , 19 )

References 

1

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

2

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

3

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

4

Pinto SM, et al. (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15, 532-44
25367039   Curated Info

5

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

6

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

7

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

8

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

9

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

10

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

11

Bonnette PC, et al. (2010) Phosphoproteomic characterization of PYK2 signaling pathways involved in osteogenesis. J Proteomics 73, 1306-20
20116462   Curated Info

12

Bruzzaniti A, et al. (2009) Dynamin reduces Pyk2 Y402 phosphorylation and SRC binding in osteoclasts. Mol Cell Biol 29, 3644-56
19380485   Curated Info

13

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

14

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

15

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

16

Miyazaki T, et al. (2004) Src kinase activity is essential for osteoclast function. J Biol Chem 279, 17660-6
14739300   Curated Info

17

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

18

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

19

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

20

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

21

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

22

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

23

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

24

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