Integrin-dependent Control of Translation: Engagement of Integrin αIIbβ3 Regulates Synthesis of Proteins in Activated Human Platelets

R Pabla, AS Weyrich, DA Dixon, PF Bray… - The Journal of cell …, 1999 - rupress.org
R Pabla, AS Weyrich, DA Dixon, PF Bray, TM McIntyre, SM Prescott, GA Zimmerman
The Journal of cell biology, 1999rupress.org
Integrins are widely expressed plasma membrane adhesion molecules that tether cells to
matrix proteins and to one another in cell–cell interactions. Integrins also transmit outside-in
signals that regulate functional responses of cells, and are known to influence gene
expression by regulating transcription. In previous studies we found that platelets, which are
naturally occurring anucleate cytoplasts, translate preformed mRNA transcripts when they
are activated by outside-in signals. Using strategies that interrupt engagement of integrin …
Integrins are widely expressed plasma membrane adhesion molecules that tether cells to matrix proteins and to one another in cell–cell interactions. Integrins also transmit outside-in signals that regulate functional responses of cells, and are known to influence gene expression by regulating transcription. In previous studies we found that platelets, which are naturally occurring anucleate cytoplasts, translate preformed mRNA transcripts when they are activated by outside-in signals. Using strategies that interrupt engagement of integrin αIIbβ3 by fibrinogen and platelets deficient in this integrin, we found that αIIbβ3 regulates the synthesis of B cell lymphoma 3 (Bcl-3) when platelet aggregation is induced by thrombin. We also found that synthesis of Bcl-3, which occurs via a specialized translation control pathway regulated by mammalian target of rapamycin (mTOR), is induced when platelets adhere to immobilized fibrinogen in the absence of thrombin and when integrin αIIbβ3 is engaged by a conformation-altering antibody against integrin αIIbβ3. Thus, outside-in signals delivered by integrin αIIbβ3 are required for translation of Bcl-3 in thrombin-stimulated aggregated platelets and are sufficient to induce translation of this marker protein in the absence of thrombin. Engagement of integrin α2β1 by collagen also triggered synthesis of Bcl-3. Thus, control of translation may be a general mechanism by which surface adhesion molecules regulate gene expression.
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