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

The affinities of integrin alpha beta heterodimers for extracellular l igands are important regulators of cell adhesion. Intracellular signal s provoke changes in the integrin extracellular domain resulting in '' activation,'' as manifested by an increase in affinity. Interactions o f 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) subu nits, 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 al pha(IIb) or of beta(3) bearing a mutation that disrupts inside out sig naling lacked inhibitory activity. These data suggest that limiting qu antities of intracellular factors bind to integrin beta(3) and beta(1) cytoplasmic domains to modulate ligand binding affinity. Structural m imics of these domains may provide a novel means to alter cell adhesio n.