Integrin-dependent control of translation: Engagement of integrin alpha(IIb)beta(3) regulates synthesis of proteins in activated human platelets

Integrins are widely expressed plasma membrane adhesion molecules that teth er cells to matrix proteins and to one another in cell-cell interactions. I ntegrins also transmit outside-in signals that regulate functional response s of cells, and are known to influence gene expression by regulating transc ription. In previous studies we found that platelets, which are naturally o ccurring anucleate cytoplasts, translate preformed mRNA transcripts when th ey are activated by outside-in signals. Using strategies that interrupt eng agement of integrin alpha(IIb)beta(3) by fibrinogen and platelets deficient in this integrin, we found that alpha(IIb)beta(3) regulates the synthesis of B cell lymphoma 3 (Bcl-3) when platelet aggregation is induced by thromb in. We also found that synthesis of Bcl-3, which occurs via a specialized t ranslation control pathway regulated by mammalian target of rapamycin (mTOR ), is induced when platelets adhere to immobilized fibrinogen in the absenc e of thrombin and when integrin alpha(IIb)beta(3) is engaged by a conformat ion-altering antibody against integrin alpha(IIb)beta(3). Thus, outside-in signals delivered by integrin alpha(IIb)beta(3) are required for translatio n of Bcl-3 in thrombin-stimulated aggregated platelets and are sufficient t o induce translation of this marker protein in the absence of thrombin. Eng agement of integrin alpha(2)beta(1) by collagen also triggered synthesis of Bcl-3. Thus, control of translation may be a general mechanism by which su rface adhesion molecules regulate gene expression.