mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets.

mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Research Abstract Details 

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mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Abstract Text:

Andrew S Weyrich,Melvin M Denis,Hansjorg Schwertz,Neal D Tolley,Jason Foulks,Eliott Spencer,Larry W Kraiss,Kurt H Albertine,Thomas M McIntyre,Guy A Zimmerman,Andrew S Weyrich,Melvin M Denis,Hansjorg Schwertz,Neal D Tolley,Jason Foulks,Eliott Spencer,Larry W Kraiss,Kurt H Albertine,Thomas M McIntyre,Guy A Zimmerman,

New activities of human platelets continue to emerge. One unexpected response is new synthesis of proteins from previously transcribed RNAs in response to activating signals. We previously reported that activated human platelets synthesize B-cell lymphoma-3 (Bcl-3) under translational control by mammalian target of rapamycin (mTOR). Characterization of the ontogeny and distribution of the mTOR signaling pathway in CD34+ stem cell-derived megakaryocytes now demonstrates that they transfer this regulatory system to developing proplatelets. We also found that Bcl-3 is required for condensation of fibrin by activated platelets, demonstrating functional significance for mTOR-regulated synthesis of the protein. Inhibition of mTOR by rapamycin blocks clot retraction by human platelets. Platelets from wild-type mice synthesize Bcl-3 in response to activation, as do human platelets, and platelets from mice with targeted deletion of Bcl-3 have defective retraction of fibrin in platelet-fibrin clots mimicking treatment of human platelets with rapamycin. In contrast, overexpression of Bcl-3 in a surrogate cell line enhanced clot retraction. These studies identify new features of post-transcriptional gene regulation and signal-dependant protein synthesis in activated platelets that may contribute to thrombus and wound remodeling and suggest that posttranscriptional pathways are targets for molecular intervention in thrombotic disorders.

mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Publishing Authors By Initials

AS Weyrich,MM Denis,H Schwertz,ND Tolley,J Foulks,E Spencer,LW Kraiss,KH Albertine,TM McIntyre,GA Zimmerman,AS Weyrich,MM Denis,H Schwertz,ND Tolley,J Foulks,E Spencer,LW Kraiss,KH Albertine,TM McIntyre,GA Zimmerman,

For similar proteins: transcription factors research abstracts see: proteins: transcription factors research

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mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Blood

VOLUME: 109

Page Numbers: 1975-83

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 16

MONTH: 11

YEAR: 2006

mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Information

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LANGUAGE: eng

NlmUniqueID: 7603509

mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: genetics

Chemical & Substance for Abstract: mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Information

Substance Name: Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets.

AFFILIATION: Department of Internal Medicine, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-75507

ACRONYM: HL

MEDLINETA: Blood

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