β3-Endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin β3 subunit

Abstract

The adhesive and signaling functions of integrins are regulated through their cytoplasmic domains. We identified a novel 111 residue polypeptide, designated β3-endonexin, that interacted with the cytoplasmic tail of the β3 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 β3 cytoplasmic tail (S752→P) that disrupts integrin signaling. Moreover, this interaction is integrin subunit specific since it was not observed with the cytoplasmic tails of the α(11b), β1, or β2 subunits. β3-Endonexin fusion proteins bound selectively to detergent-solubilized β3 from platelets and human umbilical vein endothelial cells, and β3- endonexin mRNA and protein were detected in platelets and other tissues. A related mRNA encoded a larger polypeptide that failed to bind to β integrin tails. The apparent specificity of β3-endonexin for the β3 integrin subunit suggests potential mechanisms for selective modulation of integrin functions.