ALPHA-L-BETA-2 INTEGRIN LFA-1 BINDING TO ICAM-1 INDUCED BY CYTOHESIN-1, A CYTOPLASMIC REGULATORY MOLECULE/

The avidity of integrin adhesion receptors for extracellular ligands i s subject to dynamic regulation by intracellular programs that have ye t to be elucidated. We describe here a protein, cytohesin-1, which spe cifically interacts with the intracellular portion of the integrin bet a 2 chain (CD18). The molecule shows homology to the yeast SEC7 gene p roduct and bears a pleckstrin homology (PH) domain. Overexpression of either the full-length cytohesin-1 or the SEC7 domain induces beta 2 i ntegrin-dependent binding of Jurkat cells to ICAM-1, whereas expressio n of the isolated cytohesin-1 PH domain inhibits T cell receptor-stimu lated adhesion. Similar inhibition is not exhibited by PH domains take n from other proteins, showing that the interaction is specific and th at individual PH domains are capable of discriminating between alterna tive targets.