INSIDE-OUT SIGNAL-TRANSDUCTION INHIBITED BY ISOLATED INTEGRIN CYTOPLASMIC DOMAINS

The affinities of integrin alpha beta heterodimers for extracellular ligands are important regulators of cell adhesion. Intracellular signals provoke changes in the integrin extracellular domain resulting in ''activation,'' as manifested by an increase in affinity. Interactions of integrin cytoplasmic domains with intracellular elements may mediate this ''inside-out signaling.'' Here we report that overexpression of chimeras of the cytoplasmic domain of integrin beta(3) or beta(1) subunits, joined to the extracellular and transmembrane domains of the Tac subunit of the interleukin-2 receptor, reduced integrin affinity. In contrast, chimeras containing the cytoplasmic domain of alpha(5) or alpha(IIb) or of beta(3) bearing a mutation that disrupts inside out signaling lacked inhibitory activity. These data suggest that limiting quantities of intracellular factors bind to integrin beta(3) and beta(1) cytoplasmic domains to modulate ligand binding affinity. Structural mimics of these domains may provide a novel means to alter cell adhesion.