MUTATION OF THE CYTOPLASMIC DOMAIN OF THE INTEGRIN BETA(3) SUBUNIT - DIFFERENTIAL-EFFECTS ON CELL SPREADING, RECRUITMENT TO ADHESION PLAQUES, ENDOCYTOSIS, AND PHAGOCYTOSIS

The cytoplasmic domain of the beta subunit of the alpha(IIb)beta(3) in tegrin is required for cell spreading on fibrinogen, Here we report th at deletion of six amino acids from the COOH terminus of the beta(3) ( I(757)TYRGT) totally abolished cell spreading and formation of adhesio n plaques, whereas retaining Ile(757) partially preserved these functi ons, We further found that substitution of Tyr(747) with Ala also abol ished alpha(IIb)beta(3)-mediated cell spreading.The effects of these a nd other mutations on additional functions of alpha(IIb)beta(3) were a lso studied. Progressive truncations of beta(3), in which stop codons were inserted at amino acid positions 759-756, caused partial defects in the recruitment of alpha(IIb)beta(3) to preestablished adhesion pla ques and a gradual decrease in the ability of alpha(IIb)beta(3) to med iate internalization of fibrinogen-coated particles, The Tyr(747) --> Ala substitution mutant was almost totally inactive in both of these a ssays, Point mutations at Tyr(769), and at a conserved area close to t he transmembrane domain of beta(3), decreased integrin recruitment to preestablished adhesion plaques but allowed alpha(IIb)beta(3)-mediated formation of these structures and partial cell spreading, Deletion of the cytoplasmic domain of beta(3) did not affect the constitutive end ocytosis of alpha(IIb)beta(3).