Distinct domains of alpha IIb beta 3 support different aspects of outside-in signal transduction and platelet activation induced by LSARLAF, an alphaIIb beta 3 interacting peptide

The peptide LSARLAF causes alpha II beta3-dependent platelet activation exe mplified by secretion, aggregation, spreading and adhesion on fibrinogen, a nd tyrosine phosphorylation. alpha IIb beta3-dependent outside-in signal tr ansduction induced by LSARLAF was investigated in variant thrombasthenic pl atelets which lack most of the cytoplasmic domain of the integrin beta3 sub unit ((alpha IIb beta3 Delta 724), These studies revealed that only certain aspects of this alpha IIb beta3-dependent outside-in signaling were affect ed by the beta3 truncation. Specifically, alpha IIb beta3 Delta 724 support ed LSARLAF-induced platelet aggregation, agglutination and secretion, but f ailed to trigger cytoskeletal reorganization and platelet spreading on fibr inogen. despite the fact that PMA-induced non alpha IIb beta3 mediated sign aling caused spreading of these platelets on fibrinogen. Thus, distinct dom ains of alpha IIb beta3 are required to support different aspects of LSARLA F-induced platelet activation. Furthermore, these studies suggest ;that not all alpha IIb beta3-dependent platelet responses require an intact beta3 c ytoplasmic tail.