THE ALPHA(V)BETA(3) INTEGRIN REGULATES ALPHA(5)BETA(1)-MEDIATED CELL-MIGRATION TOWARD FIBRONECTIN

This study examines the interactions of alpha(v) beta(3) and alpha(5) beta(1) in the regulation of cell migration, Human embryonic kidney (H EK) 293 cells that express alpha(5) beta(1) endogenously were transfec ted with alpha(v) beta(3) and beta(3) mutants, and their attachment an d migration to fibronectin (Fn) and vitronectin (Vn) were measured, An alpha(v) beta(3) blocking antibody and the alpha(v) beta(3) ligand cy clic G-Pen-GRGDSPC-A inhibited alpha(5) beta(1)-mediated migration tow ard Fn, but not attachment to Fn. This function was alpha(v) beta(3)-s pecific since alpha(v) beta(5) transfection and alpha(v) beta(5) block ing antibody did not produce this effect, Mutations introduced into th e beta(3) integrin subunit to dissect this phenomenon revealed the fol lowing, Disruption of the ligand binding domain by the Glanzmann throm basthenia mutation beta(3)-D119Y constitutively abolished migration to ward both Vn and Fn, and attachment to Vn but not to Fn. Insertion of the Glanzmann mutation beta(3)-S752P into the cytoplasmic domain or it s truncation (beta(3)-Delta 717) abolished binding to Vn but not to Fn , Inhibition of migration toward Fn was inhibited in these cells by al pha(v) beta(3), blocking antibody. alpha(v) beta(3)-mediated inhibitio n was, however, abolished by truncation of the transmembrane domain (b eta(3)-Delta 693). These findings demonstrate alpha(v) beta(3) regulat ion of alpha(5) beta(1)-mediated cell migration and suggest that the b eta(3) transmembrane domain is essential for this function.