Document Detail


RhoA and the function of platelet integrin alphaIIbbeta3.
MedLine Citation:
PMID:  9596668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Integrins respond to "inside-out" signals, which enable them to bind adhesive ligands, and ligand binding initiates "outside-in" signals that mediate anchorage-dependent cellular responses. RhoA is a GTPase that regulates certain actin rearrangements and transcriptional events. It has also been implicated in integrin signaling, but the exact relationship is not understood. To examine this further, platelets were incubated with C3 exoenzyme to adenine diphosphate (ADP)-ribosylate and inactivate RhoA, and the function of integrin alphaIIbbeta3 was studied. Despite inactivation of >/= 90% of RhoA, platelets exhibited normal inside-out signaling, as monitored by agonist-induced binding of a fibrinogen-mimetic anti-alphaIIbbeta3 antibody and normal fibrinogen-dependent aggregation. On the other hand, RhoA inactivation decreased the adhesion of agonist-stimulated platelets to fibrinogen (P < .04) and the formation of vinculin-rich focal adhesions in platelets that did adhere (P < .001). These effects were selective because fibrin clot retraction, a response also dependent on alphaIIbbeta3 and actin contractility, was unaffected by C3, as was the content of F-actin in resting or agonist-stimulated platelets. Similar results were obtained in a Chinese hamster ovary (CHO) cell model system of alphaIIbbeta3: C3 exoenzyme (or overexpression of dominant-negative N19RhoA) failed to influence integrin activation state, but it blocked the formation of focal adhesions in cells spread on fibrinogen. These studies establish that RhoA plays a highly selective role in alphaIIbbeta3 signaling, and they identify a subset of responses to integrin ligation that may be uniquely dependent on the actin rearrangements regulated by this GTPase.
Authors:
L Leng; H Kashiwagi; X D Ren; S J Shattil
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  91     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-06-26     Completed Date:  1998-06-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4206-15     Citation Subset:  AIM; IM    
Affiliation:
Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
ADP Ribose Transferases / metabolism
Actins / metabolism
Adenosine Diphosphate Ribose / metabolism
Animals
Blood Platelets / drug effects,  metabolism,  physiology*
Botulinum Toxins*
CHO Cells
Clot Retraction
Cricetinae
GTP-Binding Proteins / metabolism,  physiology*
Humans
Ligands
Platelet Glycoprotein GPIIb-IIIa Complex / metabolism,  physiology*
Protein Binding
Signal Transduction
Tetradecanoylphorbol Acetate / pharmacology
rhoA GTP-Binding Protein
Grant Support
ID/Acronym/Agency:
HL56595/HL/NHLBI NIH HHS; HL57900/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Botulinum Toxins; 0/Ligands; 0/Platelet Glycoprotein GPIIb-IIIa Complex; 16561-29-8/Tetradecanoylphorbol Acetate; 20762-30-5/Adenosine Diphosphate Ribose; EC 2.4.2.-/ADP Ribose Transferases; EC 2.4.2.-/exoenzyme C3, Clostridium botulinum; EC 3.6.1.-/GTP-Binding Proteins; EC 3.6.5.2/rhoA GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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