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Integrin-mediated Activation of Focal Adhesion Kinase Is Independent of Focal Adhesion Formation or Integrin Activation

1997; Elsevier BV; Volume: 272; Issue: 36 Linguagem: Inglês

10.1074/jbc.272.36.22538

1083-351X

Suzanne Lyman, Andrew Gilmore, Keith Burridge, Susan Gidwitz, Gilbert White,

Protease and Inhibitor Mechanisms

Integrin α IIb β 3 functions as the fibrinogen receptor on platelets and mediates platelet aggregation and clot retraction. Among the events that occur during either "inside-out" or "outside-in" signaling through α IIb β 3 is the phosphorylation of focal adhesion kinase (pp125 FAK ) and the association of pp125 FAK with cytoskeletal components. To examine the role of pp125 FAK in these integrin-mediated events, pp125 FAK phosphorylation and association with the cytoskeleton was determined in cells expressing two mutant forms of α IIb β 3 : α IIb β 3 (D723A/E726A), a constitutively active integrin in which the putative binding site for pp125 FAK is altered, and α IIb β 3 (F727A/K729E/F730A), in which the putative binding site for α-actinin is altered. Both mutants were expressed on the cell surface and were able to bind ligand, either spontaneously or upon activation. Whereas cells expressing α IIb β 3 (D723A/E726A) were able to form focal adhesions and stress fibers upon adherence to fibrinogen, cells expressing α IIb β 3 (F727A/K729E/F730A) adhere to fibrinogen, but had reduced focal adhesions and stress fibers. pp125 FAK is recruited to focal adhesions in adherent cells expressing α IIb β 3 (D723A/E726A) and is phosphorylated in adherent cells or in cells in suspension in the presence of fibrinogen. In adherent cells expressing α IIb β 3 (F727A/K729E/F730A), pp125 FAK was phosphorylated despite reduced formation of focal adhesions and stress fibers. We conclude that activation of pp125 FAK can be dissociated from two important events in integrin signaling, the assembly of focal adhesions in adherent cells and integrin activation following ligand occupation.