PTK2 - Focal adhesion kinase 1 - human protein (Function)
 
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Gene
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PTK2 »  Focal adhesion kinase 1   [ EC 2.7.10.2 ]  (FADK 1)
 
Protein also known as:  Protein phosphatase 1 regulatory subunit 71 (PPP1R71).
Gene name:  PTK2
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1.  
23
  • UniProtKB
Isoform  Iso 6   (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.  
24
  • UniProtKB
GO molecular function 
Actin bindingdefinition[GO:0003779]  
1
  • BHF-UCL
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
JUN kinase bindingdefinition[GO:0008432]  
1
  • BHF-UCL
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
2
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
34
  • IntAct
  • UniProtKB
  • BHF-UCL
  • HGNC
Protein kinase bindingdefinition[GO:0019901]  
1
  • UniProtKB
Isoform  Iso 6   Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • Ortholog Curator
Receptor bindingdefinition[GO:0005102]  
1
  • RefGenome
SH2 domain bindingdefinition[GO:0042169]  
1
  • UniProtKB
Signal transducer activitydefinition[GO:0004871] silver  
1
  • InterPro 2 GO
GO biological process 
Angiogenesisdefinition[GO:0001525]  
2
  • UniProtKB
  • RefGenome
Axon guidancedefinition[GO:0007411]  
1
  • UniProtKB
Cell motilitydefinition[GO:0048870]  
1
  • UniProtKB
Central nervous system neuron axonogenesisdefinition[GO:0021955] silver  
1
  • Ortholog Compara
Cytoskeleton organizationdefinition[GO:0007010]  
1
  • RefGenome
Embryo developmentdefinition[GO:0009790]  
1
  • UniProtKB
Endothelial cell migrationdefinition[GO:0043542] silver  
1
  • Ortholog Compara
Ephrin receptor signaling pathwaydefinition[GO:0048013]  
1
  • UniProtKB
Epidermal growth factor receptor signaling pathwaydefinition[GO:0007173]  
1
  • RefGenome
Establishment of cell polaritydefinition[GO:0030010]  
1
  • UniProtKB
Establishment of nucleus localizationdefinition[GO:0040023] silver  
1
  • Ortholog Compara
Extracellular matrix organizationdefinition[GO:0030198] silver  
1
  • Ortholog Compara
Growth hormone receptor signaling pathwaydefinition[GO:0060396]  
1
  • BHF-UCL
Heart morphogenesisdefinition[GO:0003007]  
1
  • UniProtKB
Innate immune responsedefinition[GO:0045087]  
1
  • RefGenome
Integrin-mediated signaling pathwaydefinition[GO:0007229]  
3
  • UniProtKB
Microtubule cytoskeleton organizationdefinition[GO:0000226] silver  
1
  • Ortholog Compara
Negative regulation of anoikisdefinition[GO:2000811]  
1
  • UniProtKB
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • UniProtKB
Negative regulation of axonogenesisdefinition[GO:0050771] silver  
1
  • Ortholog Compara
Negative regulation of cell-cell adhesiondefinition[GO:0022408]  
1
  • BHF-UCL
Negative regulation of organ growthdefinition[GO:0046621] silver  
1
  • Ortholog Compara
Negative regulation of synapse assemblydefinition[GO:0051964] silver  
1
  • Ortholog Compara
Netrin-activated signaling pathwaydefinition[GO:0038007]  
1
  • UniProtKB
Neuron migrationdefinition[GO:0001764] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • RefGenome
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
3
  • UniProtKB
  • Ortholog Curator
Placenta developmentdefinition[GO:0001890]  
1
  • UniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
2
  • BHF-UCL
  • UniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • Ortholog Curator
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552]  
1
  • UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • UniProtKB
Positive regulation of protein kinase activitydefinition[GO:0045860]  
1
  • UniProtKB
Positive regulation of protein kinase B signalingdefinition[GO:0051897]  
1
  • UniProtKB
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • UniProtKB
Positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic processdefinition[GO:2000060]  
1
  • Ortholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
2
  • UniProtKB
Regulation of cell adhesion mediated by integrindefinition[GO:0033628]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • UniProtKB
Regulation of cell shapedefinition[GO:0008360]  
2
  • UniProtKB
Regulation of cytoskeleton organizationdefinition[GO:0051493]  
1
  • UniProtKB
Regulation of endothelial cell migrationdefinition[GO:0010594]  
1
  • UniProtKB
Regulation of epithelial cell migrationdefinition[GO:0010632]  
1
  • UniProtKB
Regulation of focal adhesion assemblydefinition[GO:0051893]  
3
  • UniProtKB
Regulation of GTPase activitydefinition[GO:0043087]  
1
  • UniProtKB
Regulation of osteoblast differentiationdefinition[GO:0045667]  
1
  • UniProtKB
Regulation of protein phosphorylationdefinition[GO:0001932]  
1
  • UniProtKB
Regulation of substrate adhesion-dependent cell spreadingdefinition[GO:1900024]  
1
  • UniProtKB
Signal complex assemblydefinition[GO:0007172] silver  
1
  • InterPro 2 GO
Transforming growth factor beta receptor signaling pathwaydefinition[GO:0007179]  
1
  • UniProtKB
Vasculogenesisdefinition[GO:0001570] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
5
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-562,271.  
7
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Amoebiasis  hsa05146+5747  
Axon guidance  hsa04360+5747  
Bacterial invasion of epithelial cells  hsa05100+5747  
Chemokine signaling pathway  hsa04062+5747  
ErbB signaling pathway  hsa04012+5747  
Focal adhesion  hsa04510+5747  
Leukocyte transendothelial migration  hsa04670+5747  
Pathways in cancer  hsa05200+5747  
Regulation of actin cytoskeleton  hsa04810+5747  
Small cell lung cancer  hsa05222+5747  
VEGF signaling pathway  hsa04370+5747  
According to Reactome, this protein belongs to the following pathways:
Apoptotic cleavage of cellular proteins  REACT_107  
DCC mediated attractive signaling  REACT_22351  
EPHA-mediated growth cone collapse  REACT_264548  
EPHB-mediated forward signaling  REACT_263952  
GRB2:SOS provides linkage to MAPK signaling for Integrins  REACT_15443  
Integrin alphaIIb beta3 signaling  REACT_15523  
NCAM signaling for neurite out-growth  REACT_18334  
Netrin mediated repulsion signals  REACT_22384  
p130Cas linkage to MAPK signaling for integrins  REACT_15381  
Regulation of actin dynamics for phagocytic cup formation  REACT_160086  
Signal regulatory protein (SIRP) family interactions  REACT_23916  
VEGFA-VEGFR2 Pathway  REACT_264464  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Molecular function 
Developmental protein  definition   [KW-0217]
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PTK2
GenomeRNAi: 5747
PRO: PR:Q05397
Chemistry
GuidetoPHARMACOLOGY: 2180