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Titolo:
Integrins regulate the intracellular distribution of eukaryotic initiationfactor 4E in platelets - A checkpoint for translational control
Autore:
Lindemann, S; Tolley, ND; Eyre, JR; Kraiss, LW; Mahoney, TM; Weyrich, AS;
Indirizzi:
Univ Utah, Sch Med, Eccles Program Human Biol & Genet, Salt Lake City, UT 84112 USA Univ Utah Salt Lake City UT USA 84112 Genet, Salt Lake City, UT 84112 USA Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84112 USA Univ Utah Salt Lake City UT USA 84112 l Med, Salt Lake City, UT 84112 USA Univ Utah, Sch Med, Dept Surg, Salt Lake City, UT 84112 USA Univ Utah Salt Lake City UT USA 84112 Surg, Salt Lake City, UT 84112 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 36, volume: 276, anno: 2001,
pagine: 33947 - 33951
SICI:
0021-9258(20010907)276:36<33947:IRTIDO>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANCHORAGE-DEPENDENT FIBROBLASTS; ACTIVATED HUMAN PLATELETS; HUMAN-BLOOD PLATELETS; MESSENGER-RNA; MEMBRANE SKELETON; PROTEIN-SYNTHESIS; CYTOSKELETON; RIBOSOMES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Weyrich, AS Univ Utah, Sch Med, Eccles Program Human Biol & Genet, Biol 533,Rm 4220, Salt Lake City, UT 84112 USA Univ Utah Biol 533,Rm 4220 Salt Lake City UT USA 84112 112 USA
Citazione:
S. Lindemann et al., "Integrins regulate the intracellular distribution of eukaryotic initiationfactor 4E in platelets - A checkpoint for translational control", J BIOL CHEM, 276(36), 2001, pp. 33947-33951

Abstract

Recent evidence from our laboratory demonstrates that platelets synthesizenumerous proteins in a signal-dependent fashion (Pabla, R., Weyrich, A. S., Dixon, D. A., Bray, P. F., McIntyre, T. M., Prescott, S. M., and Zimmerman, G. A. (1999) J. Cell Biol. 144, 175-184; Weyrich, A. S., Dixon, D. A., Pabla, R., Elstad, M. R., McIntyre, T. M., Prescott, S. M., and Zimmerman, G. A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 5556-5561). Protein synthesis in platelets is controlled at the translational level; however, the mechanisms of regulation are not known. Here we demonstrate that translation initiation factors are redistributed to mRNA-rich areas in aggregated platelets, an event that induces protein synthesis. Interrogation of cDNA arrays revealed that platelet-derived mRNAs are primarily associated with the cytoskeletal core. In contrast, eukaryotic initiation factor 4E (eIF4E), the essential mRNA cap-binding protein that controls global translation rates, is localized in the membrane skeleton and soluble fraction of platelets, physically separated from most mRNAs. Platelet activation redistributes eIF4E tothe cytoskeleton and increases interactions of eIF4E with mRNA cap structures. Redistribution of eIF4E to the mRNA-rich cytoskeleton coincides with amarked increase in protein synthesis, a process that is blocked when intracellular actin is disrupted. Additional studies demonstrated that ss (3) integrins are the primary membrane receptor that distributes eIF4E within thecell. These results imply that integrins link receptor-mediated pathways with mRNA-rich cytoskeletal domains and thereby modulate the organization ofintracellular translational complexes. They also indicate that the functional status of eIF4E is regulated by its intracellular distribution.

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Documento generato il 23/01/20 alle ore 18:24:07