BETA(3)-ENDONEXIN, A NOVEL POLYPEPTIDE THAT INTERACTS SPECIFICALLY WITH THE CYTOPLASMIC TAIL OF THE INTEGRIN-BETA(3) SUBUNIT

The adhesive and signaling functions of integrins are regulated throug h their cytoplasmic domains. We identified a novel 111 residue polypep tide, designated beta(3)-endonexin, that interacted with the cytoplasm ic tail of the beta(3) integrin subunit in a yeast two-hybrid system. This interaction is structurally specific, since it was reduced by 64% by a point mutation in the beta(3) cytoplasmic tail (S-752-->P) that disrupts integrin signaling. Moreover, this interaction is integrin su bunit specific since it was not observed with the cytoplasmic tails of the alpha(IIb), beta(1), or beta(2) subunits. beta(3)-Endonexin fusio n proteins bound selectively to detergent-solubilized beta(3) from pla telets and human umbilical vein endothelial cells, and beta(3)-endonex in mRNA and protein were detected in platelets and other tissues. A re lated mRNA encoded a larger polypeptide that failed to bind to beta in tegrin tails. The apparent specificity of beta(3)-endonexin for the be ta(3) integrin subunit suggests potential mechanisms for selective mod ulation of integrin functions.