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© The Rockefeller University Press, 0021-9525/1999//175 $5.00
The Journal of Cell Biology, Volume 144, Number 1, , 1999 175-184

Article

Integrin-dependent Control of Translation: Engagement of Integrin {alpha}IIbβ3 Regulates Synthesis of Proteins in Activated Human Platelets



Ravinder Pabla*, Andrew S. Weyrich*,||, Dan A. Dixon{ddagger}, Paul F. Bray**, Thomas M. McIntyre*,||,¶, Stephen M. Prescott{ddagger},§,||, and Guy A. Zimmerman*,||

* Nora Eccles Harrison Cardiovascular Research and Training Institute, {ddagger} Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, § Department of Biochemistry, || Department of Internal Medicine, and Department of Pathology, University of Utah, Salt Lake City, Utah 84112; and the ** Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

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 {alpha}IIbβ3 by fibrinogen and platelets deficient in this integrin, we found that {alpha}IIbβ3 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 {alpha}IIbβ3 is engaged by a conformation-altering antibody against integrin {alpha}IIbβ3. Thus, outside-in signals delivered by integrin {alpha}IIbβ3 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 {alpha}2β1 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.

Key Words: adhesion • integrins • platelets • translation • gene regulation

Abbreviations used in this paper: Bcl-3, B cell lymphoma 3; mTOR, mammalian target of rapamycin; PDK1, 3-phosphoinositide-dependent protein kinase 1; PI3K, phosphatidylinositol-3-kinase.


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