Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets

AS Weyrich, DA Dixon, R Pabla… - Proceedings of the …, 1998 - National Acad Sciences
AS Weyrich, DA Dixon, R Pabla, MR Elstad, TM McIntyre, SM Prescott, GA Zimmerman
Proceedings of the National Academy of Sciences, 1998National Acad Sciences
Circulating human platelets lack nuclei, cannot synthesize mRNA, and are considered
incapable of regulated protein synthesis. We found that thrombin-activated, but not resting,
platelets synthesize Bcl-3, a member of the IκB-α family of regulatory proteins. The time-and
concentration-dependent generation of Bcl-3 in platelets signaled by thrombin was blocked
by translational inhibitors, by rapamycin, and by inhibitors of phosphatidylinositol-3-kinase,
indicating that it occurs via a specialized translational control pathway that involves …
Circulating human platelets lack nuclei, cannot synthesize mRNA, and are considered incapable of regulated protein synthesis. We found that thrombin-activated, but not resting, platelets synthesize Bcl-3, a member of the IκB-α family of regulatory proteins. The time- and concentration-dependent generation of Bcl-3 in platelets signaled by thrombin was blocked by translational inhibitors, by rapamycin, and by inhibitors of phosphatidylinositol-3-kinase, indicating that it occurs via a specialized translational control pathway that involves phosphorylation of the inhibitory protein 4E-BP1. After its synthesis in activated platelets Bcl-3 binds to the SH3 domain of Fyn (p59fyn), a Src-related tyrosine kinase. This, along with its expression in anucleate cells, suggests that Bcl-3 has previously unrecognized functions aside from modulation of transcription. We also demonstrate that platelets synthesize and secrete numerous proteins besides Bcl-3 after they adhere to fibrinogen, which mediates adhesion and outside–in signaling of these cells by engagement of αIIb/β3 integrin. Taken together, these data demonstrate that regulated synthesis of proteins is a signal-dependent activation response of human platelets.
National Acad Sciences