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

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 IkappaB-alpha 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 (p59(fyn)), 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 alphaIIb/beta3 integrin. Taken together, these data demonstrate that regulated synthesis of proteins is a signal-dependent activation response of human platelets.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Blood Platelets, Carrier Proteins, Enzyme Inhibitors, Humans, Peptide Initiation Factors, Phosphoproteins, Phosphorylation, Platelet Activation, Polyenes, Polymerase Chain Reaction, Protein Biosynthesis, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Repressor Proteins, Signal Transduction, Sirolimus, Transcription Factors, Transfection, src Homology Domains
Proc. Natl. Acad. Sci. U.S.A.
Date: May. 12, 1998
Download Curated Data For This Publication
1092
Switch View:
  • Interactions 1