Reaction known_transition_omitted e_re978 map

FAK1*|​emp@Cytoplasm map FAK1*|​pho@Cytoplasm map

Reaction regulators:

  1. EGF family*:​EGFR family*|​pho|​hm2@Cytoplasm map
  1. ITGB1@Cytoplasm map
  2. ITGA8:​ITGB1@Cytoplasm map
  3. (ITGA5:​ITGB1)|​active@Extracellular space map
  4. (ITGAV:​ITGB3)|​active@Extracellular space map
  5. PXN@Cytoplasm map
  6. Vinculin*@Cytoplasm map
  7. Talin*@Cytoplasm map

Autophosphorylation of PTK2:
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.
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.


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