Document Detail


Differential phosphorylation of myosin light chain (Thr)18 and (Ser)19 and functional implications in platelets.
MedLine Citation:
PMID:  20670370     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Myosin IIA is an essential platelet contractile protein that is regulated by phosphorylation of its regulatory light chain (MLC) on residues (Thr)18 and (Ser)19 via the myosin light chain kinase (MLCK).
OBJECTIVE: The present study was carried out to elucidate the mechanisms regulating MLC (Ser)19 and (Thr)18 phosphorylation and the functional consequence of each phosphorylation event in platelets.
RESULTS: Induction of 2MeSADP-induced shape change occurs within 5s along with robust phosphorylation of MLC (Ser)19 with minimal phosphorylation of MLC (Thr)18. Selective activation of G(12/13) produces both slow shape change and comparably slow MLC (Thr)18 and (Ser)19 phosphorylation. Stimulation with agonists that trigger ATP secretion caused rapid MLC (Ser)19 phosphorylation while MLC (Thr)18 phosphorylation was coincident with secretion. Platelets treated with p160(ROCK) inhibitor Y-27632 exhibited a partial inhibition in secretion and had a substantial inhibition in MLC (Thr)18 phosphorylation without effecting MLC (Ser)19 phosphorylation. These data suggest that phosphorylation of MLC (Ser)19 is downstream of Gq/Ca(2+) -dependent mechanisms and sufficient for shape change, whereas MLC (Thr)18 phosphorylation is substantially downstream of G(12/13) -regulated Rho kinase pathways and necessary, probably in concert with MLC (Ser)19 phosphorylation, for full contractile activity leading to dense granule secretion. Overall, we suggest that the amplitude of the platelet contractile response is differentially regulated by a least two different signaling pathways, which lead to different phosphorylation patterns of the myosin light chain, and this mechanism results in a graded response rather than a simple on/off switch.
Authors:
T M Getz; C A Dangelmaier; J Jin; J L Daniel; S P Kunapuli
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  8     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-28     Completed Date:  2011-03-07     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  2283-93     Citation Subset:  IM    
Copyright Information:
© 2010 International Society on Thrombosis and Haemostasis.
Affiliation:
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / chemistry
Blood Platelets / metabolism*
Calcium / chemistry,  metabolism
Cell Shape
Humans
Kinetics
Myosin Light Chains / chemistry*,  genetics*
Phosphorylation
Platelet Aggregation
Serine / chemistry*
Signal Transduction
Threonine / chemistry*
rho-Associated Kinases / metabolism
Grant Support
ID/Acronym/Agency:
HL07777/HL/NHLBI NIH HHS; HL60683/HL/NHLBI NIH HHS; HL80444/HL/NHLBI NIH HHS; HL81322/HL/NHLBI NIH HHS; R01 HL060683-13/HL/NHLBI NIH HHS; R01 HL081322-05/HL/NHLBI NIH HHS; R01 HL093231-03/HL/NHLBI NIH HHS; R01 HL093231-04/HL/NHLBI NIH HHS; T32 HL007777-17/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Myosin Light Chains; 56-45-1/Serine; 58-64-0/Adenosine Diphosphate; 72-19-5/Threonine; 7440-70-2/Calcium; EC 2.7.11.1/rho-Associated Kinases
Comments/Corrections

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