The activation state of the integrin alpha IIb beta 3 affects outside-in signals leading to cell spreading and focal adhesion kinase phosphorylation.

Pelletier AJ, Kunicki T, Ruggeri ZM, Quaranta V
J Biol Chem. 1995 270 (30): 18133-40

PMID: 7543096 · DOI:10.1074/jbc.270.30.18133

Integrins bind extracellular matrix and transduce signals mediating cell adhesion, spreading, and migration. It is unclear how these distinct responses follow from a common event: integrin clustering. We examined the relationship between integrin-mediated signals and the integrin's activation state using a cell line expressing alpha IIb beta 3 (Clone B) and a panel of monoclonal antibodies against this integrin. Non-activating antibodies used to cluster alpha IIb beta 3 stimulated focal adhesion kinase (FAK) phosphorylation, regardless of affinity, subunit specificity, or ligand-blocking phenotype. Coated on plastic, these antibodies supported cell adhesion, spreading, and FAK phosphorylation. In contrast, clustering of alpha IIb beta 3 induced with activating antibodies, or binding of soluble fibrinogen to antibody-activated alpha IIb beta 3, did not induce FAK phosphorylation. Thus, clustering of alpha IIb beta 3 on Clone B does not necessarily result in FAK phosphorylation. Coated on plastic, activating antibodies supported cell adhesion, but not spreading or FAK phosphorylation. Therefore, it appears the resting, not the active form of alpha IIb beta 3, induces cell spreading and FAK phosphorylation in Clone B. These data indicate that "inside-out" signals may alter not only the binding specificity of an integrin, but the "outside-in" biochemical signals that integrin initiates as well. This activation state-linked signaling represents a novel mechanism, which may explain how diverse cellular responses are induced by integrin-matrix interactions.

MeSH Terms (16)

Antibodies, Monoclonal Cell Adhesion Cell Adhesion Molecules Cell Line, Transformed Cell Movement Fibrinogen Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Humans Integrins Phosphorylation Phosphotyrosine Platelet Glycoprotein GPIIb-IIIa Complex Protein-Tyrosine Kinases Signal Transduction Tyrosine

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