Tyr428

Site Information
SGDETDDyAEIIDEE SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447887

In vivo Characterization
Methods used to characterize site in vivo:	immunoprecipitation ( 1 , 3 , 12 , 15 , 33 ) , mass spectrometry ( 3 ) , mutation of modification site ( 3 , 17 , 18 , 21 , 25 , 33 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 27 , 29 , 30 , 31 , 33 )
Disease tissue studied:	breast cancer ( 24 ) , cervical cancer ( 5 ) , cervical squamous cell carcinoma ( 5 ) , liver cancer ( 12 ) , squamous cell carcinoma of the liver ( 12 ) , lung cancer ( 1 ) , non-small cell lung cancer ( 1 ) , non-small cell lung adenocarcinoma ( 1 ) , cancer, squamous cell carcinoma ( 7 ) , testicular cancer ( 23 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' [PCDHGA1 (mouse), homozygous knockout] ( 6 ) , 'brain, hippocampus' ( 32 ) , 'neuron, hippocampal'-'brain, embryonic' ( 17 ) , 'renal, podocyte' ( 2 ) , 293F (epithelial) ( 19 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 31 ) , 3T3 (fibroblast) ( 16 , 24 ) , B lymphocyte ( 20 ) , BaF3 ('B lymphocyte, precursor') [PXN (mouse)] ( 27 ) , bone marrow ( 3 ) , C2C12 (myoblast) ( 25 ) , CaSki (cervical) ( 5 ) , COS (fibroblast) ( 24 , 33 ) , embryo ( 11 ) , endothelial ( 13 ) , fibroblast-skin ( 18 ) , GD25 (fibroblast) ( 28 , 30 ) , HCC827 (pulmonary) ( 1 ) , keratinocyte-skin ( 19 ) , MA-10 (testicular) ( 23 ) , MDA-MB-435 (breast cell) ( 24 ) , MEF (fibroblast) [IGF1R (mouse)] ( 26 ) , MEF (fibroblast) ( 1 , 8 , 11 , 15 , 21 , 22 , 24 ) , NCI-H1299 (pulmonary) ( 1 ) , NCI-H1650 (pulmonary) ( 1 ) , neuron-'brain, hippocampus' ( 14 ) , platelet-blood ( 10 ) , reticulocyte ( 4 ) , SiHa (squamous) ( 5 ) , squamous ( 12 ) , squamous [FAK iso2 (mouse), homozygous knockout] ( 7 ) , Swiss 3T3 (fibroblast) ( 29 )

Upstream Regulation
Regulatory protein:	ACF7 (mouse) ( 19 ) , EZH2 (mouse) ( 3 ) , FAK iso2 (mouse) ( 11 ) , GRB7 (human) ( 16 ) , PCDHGA1 (mouse) ( 6 ) , PDPN (mouse) ( 4 ) , PTPRA (mouse) ( 22 ) , PXN (mouse) ( 8 )
Putative in vivo kinases:	FAK iso2 (mouse) ( 25 , 27 )
Putative upstream phosphatases:	DUSP3 (mouse) ( 1 ) , STS-1 (mouse) ( 10 )
Phosphatases, in vitro:	DUSP3 (human) ( 1 ) , STS-1 (mouse) ( 10 )
Treatments:	2-AG ( 32 ) , anandamide ( 32 ) , antibody ( 30 ) , blebbistatin ( 15 ) , bombesin ( 29 ) , cell_adhesion ( 8 , 19 , 23 , 24 , 26 , 28 ) , chorionic_gonadotropin ( 23 ) , convulxin ( 10 ) , CXCL12 ( 20 ) , dronabinol ( 32 ) , EGF ( 23 , 29 ) , ephrin_B2 ( 17 ) , fibronectin ( 2 , 11 , 12 ) , H2O2 ( 22 ) , IL-3 ( 27 ) , lactacystin ( 24 ) , laminin-1 ( 2 ) , LPA ( 9 ) , MG132 ( 20 , 24 ) , PF271 ( 15 ) , phorbol_ester ( 27 ) , PP2 ( 15 , 21 ) , PP3 ( 21 ) , rimonabant ( 32 ) , Sem3A ( 14 ) , serum_starvation ( 25 ) , TNF ( 21 ) , vasopressin ( 29 ) , Y27632 ( 4 )

Downstream Regulation
Effects of modification on FAK iso2:	activity, induced ( 21 , 27 ) , enzymatic activity, induced ( 11 , 17 , 33 ) , molecular association, regulation ( 12 )
Effects of modification on biological processes:	carcinogenesis, induced ( 5 ) , cell adhesion, altered ( 1 , 20 , 33 ) , cell adhesion, induced ( 7 , 18 ) , cell growth, induced ( 8 ) , cell motility, altered ( 11 ) , cell motility, induced ( 5 , 8 ) , cytoskeletal reorganization ( 17 ) , signaling pathway regulation ( 17 ) , transcription, altered ( 21 )
Induce interaction with:	PLCG1 (human) ( 33 ) , Src iso1 (mouse) ( 12 )

References
1	Chen YR, et al. (2017) Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration. Oncogene 36, 6509-6517 28759036 Curated Info
2	Verma R, et al. (2016) Integrin Ligation Results in Nephrin Tyrosine Phosphorylation In Vitro. PLoS One 11, e0148906 26848974 Curated Info
3	Gunawan M, et al. (2015) The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin. Nat Immunol 16, 505-16 25751747 Curated Info
4	Kumar V, et al. (2015) A dendritic-cell-stromal axis maintains immune responses in lymph nodes. Immunity 42, 719-30 25902483 Curated Info
5	Chiu CF, et al. (2012) Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts. Cancer Lett 320, 205-14 22388104 Curated Info
6	Garrett AM, Schreiner D, Lobas MA, Weiner JA (2012) γ-protocadherins control cortical dendrite arborization by regulating the activity of a FAK/PKC/MARCKS signaling pathway. Neuron 74, 269-76 22542181 Curated Info
7	Sandilands E, et al. (2012) Autophagic targeting of Src promotes cancer cell survival following reduced FAK signalling. Nat Cell Biol 14, 51-60 22138575 Curated Info
8	Wade R, Brimer N, Lyons C, Vande Pol S (2011) Paxillin enables attachment-independent tyrosine phosphorylation of focal adhesion kinase and transformation by RAS. J Biol Chem 286, 37932-44 21900245 Curated Info
9	Wang Y, et al. (2011) Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction. J Biol Chem 286, 18190-201 21454597 Curated Info
10	Chen X, et al. (2010) Determination of the substrate specificity of protein-tyrosine phosphatase TULA-2 and identification of Syk as a TULA-2 substrate. J Biol Chem 285, 31268-76 20670933 Curated Info
11	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
12	Serrels B, et al. (2010) A complex between FAK, RACK1, and PDE4D5 controls spreading initiation and cancer cell polarity. Curr Biol 20, 1086-92 20493699 Curated Info
13	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
14	Chacón MR, Fernández G, Rico B (2010) Focal adhesion kinase functions downstream of Sema3A signaling during axonal remodeling. Mol Cell Neurosci 44, 30-42 20159040 Curated Info
15	Pasapera AM, et al. (2010) Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylation. J Cell Biol 188, 877-90 20308429 Curated Info
16	Chu PY, et al. (2009) Tyrosine Phosphorylation of Growth Factor Receptor-bound Protein-7 by Focal Adhesion Kinase in the Regulation of Cell Migration, Proliferation, and Tumorigenesis. J Biol Chem 284, 20215-26 19473962 Curated Info
17	Shi Y, et al. (2009) Focal adhesion kinase acts downstream of EphB receptors to maintain mature dendritic spines by regulating cofilin activity. J Neurosci 29, 8129-42 19553453 Curated Info
18	Michael KE, et al. (2009) Focal adhesion kinase modulates cell adhesion strengthening via integrin activation. Mol Biol Cell 20, 2508-19 19297531 Curated Info
19	Wu X, Kodama A, Fuchs E (2008) ACF7 regulates cytoskeletal-focal adhesion dynamics and migration and has ATPase activity. Cell 135, 137-48 18854161 Curated Info
20	Le Y, et al. (2007) SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis. Immunity 27, 811-23 18031698 Curated Info
21	Schlaepfer DD, et al. (2007) Tumor necrosis factor-alpha stimulates focal adhesion kinase activity required for mitogen-activated kinase-associated interleukin 6 expression. J Biol Chem 282, 17450-9 17438336 Curated Info
22	Hao Q, Rutherford SA, Low B, Tang H (2006) Selective regulation of hydrogen peroxide signaling by receptor tyrosine phosphatase-alpha. Free Radic Biol Med 41, 302-10 16814111 Curated Info
23	Mizutani T, Shiraishi K, Welsh T, Ascoli M (2006) Activation of the lutropin/choriogonadotropin receptor in MA-10 cells leads to the tyrosine phosphorylation of the focal adhesion kinase by a pathway that involves Src family kinases. Mol Endocrinol 20, 619-30 16293639 Curated Info
24	Holcomb M, Rufini A, Barilà D, Klemke RL (2006) Deregulation of proteasome function induces Abl-mediated cell death by uncoupling p130CAS and c-CrkII. J Biol Chem 281, 2430-40 16267043 Curated Info
25	Clemente CF, Corat MA, Saad ST, Franchini KG (2005) Differentiation of C2C12 myoblasts is critically regulated by FAK signaling. Am J Physiol Regul Integr Comp Physiol 289, R862-70 15890789 Curated Info
26	del Pozo MA, et al. (2005) Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nat Cell Biol 7, 901-8 16113676 Curated Info
27	Romanova LY, et al. (2004) Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and motility of lymphoid cells and is PMA-sensitive. J Cell Sci 117, 3759-68 15252114 Curated Info
28	Armulik A, Velling T, Johansson S (2004) The integrin beta1 subunit transmembrane domain regulates phosphatidylinositol 3-kinase-dependent tyrosine phosphorylation of Crk-associated substrate. Mol Biol Cell 15, 2558-67 15034138 Curated Info
29	Sinnett-Smith J, et al. (2004) Protein kinase D potentiates DNA synthesis induced by Gq-coupled receptors by increasing the duration of ERK signaling in swiss 3T3 cells. J Biol Chem 279, 16883-93 14963034 Curated Info
30	Pankov R, et al. (2003) Specific beta1 integrin site selectively regulates Akt/protein kinase B signaling via local activation of protein phosphatase 2A. J Biol Chem 278, 18671-81 12637511 Curated Info
31	Lim Y, Han I, Kwon HJ, Oh ES (2002) Trichostatin A-induced detransformation correlates with decreased focal adhesion kinase phosphorylation at tyrosine 861 in ras-transformed fibroblasts. J Biol Chem 277, 12735-40 11821402 Curated Info
32	Derkinderen P, et al. (2001) Dual role of Fyn in the regulation of FAK+6,7 by cannabinoids in hippocampus. J Biol Chem 276, 38289-96 11468287 Curated Info
33	Zhang X, et al. (1999) Focal adhesion kinase promotes phospholipase C-gamma1 activity. Proc Natl Acad Sci U S A 96, 9021-6 10430888 Curated Info