SIGNAL-DEPENDENT TRANSLATION OF A REGULATORY PROTEIN, BCL-3, IN ACTIVATED HUMAN PLATELETS

Circulating human platelets lack nuclei, cannot synthesize mRNA, and a re considered incapable of regulated protein synthesis. We found that thrombin-activated, but not resting, platelets synthesize Bcl-3, a mem ber of the I kappa B-alpha family of regulatory proteins. The time- an d concentration-dependent generation of Bcl-3 in platelets signaled by thrombin was blocked by translational inhibitors, by rapamycin, and b y inhibitors of phosphatidylinositol-3-kinase, indicating that it occu rs via a specialized translational control pathway that involves phosp horylation of the inhibitory protein 4E-BP1. After its synthesis in ac tivated platelets Bcl-3 binds to the SH3 domain of Fyn (p59(fyn)), a S rc-related tyrosine kinase, This, along with its expression in anuclea te cells, suggests that Bcl-3 has previously unrecognized functions as ide from modulation of transcription, We also demonstrate that platele ts synthesize and secrete numerous proteins besides Bcl-3 after they a dhere to fibrinogen, which mediates adhesion and outside-in signaling of these cells by engagement of alpha IIb/beta 3 integrin, Taken toget her, these data demonstrate that regulated synthesis of proteins is a signal-dependent activation response of human platelets.