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 through their cytoplasmic domains. We identified a novel 111 residue polypeptide, designated beta(3)-endonexin, that interacted with the cytoplasmic 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 subunit specific since it was not observed with the cytoplasmic tails of the alpha(IIb), beta(1), or beta(2) subunits. beta(3)-Endonexin fusion proteins bound selectively to detergent-solubilized beta(3) from platelets and human umbilical vein endothelial cells, and beta(3)-endonexin mRNA and protein were detected in platelets and other tissues. A related mRNA encoded a larger polypeptide that failed to bind to beta integrin tails. The apparent specificity of beta(3)-endonexin for the beta(3) integrin subunit suggests potential mechanisms for selective modulation of integrin functions.