FAK1*

Protein FAK1* map

Identifiers
protein tyrosine kinase 2
“PTK2 protein tyrosine kinase 2″
HUGO:PTK2 HGNC:9611 ENTREZ:5747 UNIPROT:Q05397 GENECARDS:PTK2 REACTOME:54648 KEGG:5747 ATLASONC:PTK2ID41898ch8q24 WIKI:PTK2

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 EMT  map  / CELL_MATRIX_ADHESIONS  map

FAK1*|​emp@Cytoplasm

References
e_re978( EMT  map ):
Autophosphorylation of PTK2:
PMID:7529872
PMID:19339212
PMID:7657702
PMID:16919435
FAK (PTK2) is first recruited to sites of integrin clustering via interactions wiith integrin-associated proteins such as talin, paxillin.
FAK binds to the cytoplasmic domain of b1 integrin via Paxillin (PXN) and Talin (TLN)
Binding to aVb3 or a5b1 integrins induces PTK2 (FAK1) autophosphorylation at Y397.
PMID:10545505
FAK associates with paxillin, vinculin, and p130cas (BCAR1) in the focal adhesion complex
Integrins control motile strategy through a Rho-cofilin pathway.
beta1 integrins promote random migration, whereas beta3 integrins promote persistent migration in the same epithelial cell background.
Adhesion to fibronectin by aVb3 supports actin cytoskeletal reorganization via cofilin, resulting in a single broad lamellipod with static cell-matrix adhesions at the leading edge.
Adhesion by a5b1 instead leads to the phosphorylation and thus inactivation of cofilin, and these cells fail to polarize their cytoskeleton but extend thin protrusions containing highly dynamic cell-matrix adhesions in multiple directions.
The activity of the small GTPase RhoA is particularly high in cells adhering by a5b1, and inhibition of Rho signaling causes a switch from a beta1 to a beta3-associated mode of migration, whereas increased Rho activity has the opposite effect.
Alterations in integrin expression profiles thus allow cells to modulate several critical aspects of the motile machinery through Rho GTPases.

FAK1*|​Y_pho|​pho|​active@Cytoplasm

References
e_re977( EMT  map ):
Autophosphorylation of PTK2:
PMID:7529872
PMID:19339212
PMID:7657702
PMID:16919435
Autophosphorylation of PTK2 at Y397 creates binding site for CSK, a member of Scr family kinases.
In response to integrin engagement with the ECM, FAK is autophosphorylated predominantly on Y397
This Y397 is the consensus binding site for the SH2 domain of c-Src (CSK)
PMID:11114741
Interaction of CSK with FAK leads to phosphorylation of FAK on other tyrosine residues including Y407, 576, 577, 861, 925/
These phosphorylation events promote PTK2 to its maximal catalytic activity.
Upon autophosphorylation of FAK, a signaling complex of FAK, CSK binds to and can phosphorylate various adaptor proteins such as p130Cas and paxillin.
e_re991( EMT  map ):
PMID:15688067
Alpha-actinin is a cytoskeletal protein that binds to viculin (VCL).
Via this binding, Alpha-actinin crosslinks actin (in actomyosin stress fibres) and tether them to the focal contacts.
Phosphorylation of alpha-actinin by FAK1 (PTK2) reduces the crossliking of stress fibres and prevents the maturation of focal contacts.

FAK1*|​pho@Cytoplasm

References
e_re978( EMT  map ):
Autophosphorylation of PTK2:
PMID:7529872
PMID:19339212
PMID:7657702
PMID:16919435
FAK (PTK2) is first recruited to sites of integrin clustering via interactions wiith integrin-associated proteins such as talin, paxillin.
FAK binds to the cytoplasmic domain of b1 integrin via Paxillin (PXN) and Talin (TLN)
Binding to aVb3 or a5b1 integrins induces PTK2 (FAK1) autophosphorylation at Y397.
PMID:10545505
FAK associates with paxillin, vinculin, and p130cas (BCAR1) in the focal adhesion complex
Integrins control motile strategy through a Rho-cofilin pathway.
beta1 integrins promote random migration, whereas beta3 integrins promote persistent migration in the same epithelial cell background.
Adhesion to fibronectin by aVb3 supports actin cytoskeletal reorganization via cofilin, resulting in a single broad lamellipod with static cell-matrix adhesions at the leading edge.
Adhesion by a5b1 instead leads to the phosphorylation and thus inactivation of cofilin, and these cells fail to polarize their cytoskeleton but extend thin protrusions containing highly dynamic cell-matrix adhesions in multiple directions.
The activity of the small GTPase RhoA is particularly high in cells adhering by a5b1, and inhibition of Rho signaling causes a switch from a beta1 to a beta3-associated mode of migration, whereas increased Rho activity has the opposite effect.
Alterations in integrin expression profiles thus allow cells to modulate several critical aspects of the motile machinery through Rho GTPases.
e_re977( EMT  map ):
Autophosphorylation of PTK2 at Y397 creates binding site for CSK, a member of Scr family kinases.
In response to integrin engagement with the ECM, FAK is autophosphorylated predominantly on Y397
This Y397 is the consensus binding site for the SH2 domain of c-Src (CSK)
PMID:11114741
Interaction of CSK with FAK leads to phosphorylation of FAK on other tyrosine residues including Y407, 576, 577, 861, 925/
These phosphorylation events promote PTK2 to its maximal catalytic activity.
Upon autophosphorylation of FAK, a signaling complex of FAK, CSK binds to and can phosphorylate various adaptor proteins such as p130Cas and paxillin.


Modifications:
In compartment: Cytoplasm
  1. FAK1*|​emp@Cytoplasm map

  2. FAK1*|​pho@Cytoplasm map
  3. FAK1*|​Y_pho|​pho|​active@Cytoplasm map

Participates in complexes:
In compartment: Cytoplasm

  1. FAK1*|​Y_pho|​pho:​c-SRC*@Cytoplasm map

  2. BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  3. Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  4. Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​ZYX:​c-SRC*@Cytoplasm map
  5. ARP2_3*:​Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map

Participates in reactions:
As Reactant or Product:

  1. FAK1*|​Y_pho|​pho|​active@Cytoplasm map map FAK1*|​pho@Cytoplasm map

  2. Talin partners*@Cytoplasm map map FAK1*|​Y_pho|​pho|​active@Cytoplasm map
  3. Src family kinases*@Cytoplasm map map FAK1*|​emp@Cytoplasm map
  4. FAK1*|​pho@Cytoplasm map map FAK1*|​Y_pho|​pho|​active@Cytoplasm map
  5. FAK1*|​emp@Cytoplasm map map FAK1*|​pho@Cytoplasm map
  6. FAK1*|​Y_pho|​pho|​active@Cytoplasm map + c-SRC*|​Y_pho|​active@Cytoplasm map map FAK1*|​Y_pho|​pho:​c-SRC*@Cytoplasm map
  7. FAK1*|​Y_pho|​pho:​c-SRC*@Cytoplasm map + BCAR1@Cytoplasm map + Talin*@Cytoplasm map + PXN|​pho@Cytoplasm map + Vinculin*@Cytoplasm map map BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  8. BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map + Actinin*@Cytoplasm map + Actin cytoskeletal*@Cytoplasm map map Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  9. Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map + ZYX@Cytoplasm map map Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​ZYX:​c-SRC*@Cytoplasm map
  10. ARP2_3*@Cytoplasm map + Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map map ARP2_3*:​Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map
  11. ARP2_3*:​Actin cytoskeletal*:​Actinin*:​BCAR1:​FAK1*|​Y_pho|​pho:​PXN|​pho:​Talin*:​Vinculin*:​c-SRC*@Cytoplasm map map Actin polymerization@Nucleus map

As Catalyser:

  1. PXN@Cytoplasm map map PXN|​pho@Cytoplasm map

  2. Actinin*@Cytoplasm map map Actinin*|​pho@Cytoplasm map

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