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

Please wait, while we are loading the content...

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

Content Provider	Scilit
Author	Weyrich, Andrew S. Denis, Melvin M. Schwertz, Hansjorg Tolley, Neal D. Foulks, Jason Spencer, Eliott Kraiss, Larry W. Albertine, Kurt H. McIntyre, Thomas M. Zimmerman, Guy A.
Copyright Year	2006
Description	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.
Related Links	http://www.bloodjournal.org/content/109/5/1975.full.pdf
Ending Page	1983
Page Count	9
Starting Page	1975
DOI	10.1182/blood-2006-08-042192
Journal	Blood
Issue Number	5
Volume Number	109
Language	English
Publisher	American Society of Hematology
Publisher Date	2006-11-16
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Mtor Signaling Pathway Activated Human Human Platelets Fibrin Mice Activated Platelets Thrombus Retraction Journal: Blood (Vol- 84, Issue- 5)
Content Type	Text
Resource Type	Article

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in