Document Detail

RNA interference elucidates the role of focal adhesion kinase in HLA class I-mediated focal adhesion complex formation and proliferation in human endothelial cells.
MedLine Citation:
PMID:  17548629     Owner:  NLM     Status:  MEDLINE    
Ligation of class I molecules by anti-HLA Ab stimulates an intracellular signaling cascade resulting in endothelial cell (EC) survival and proliferation, and has been implicated in the process of chronic allograft rejection and transplant-associated vasculopathy. In this study, we used small interfering RNA blockade of focal adhesion kinase (FAK) protein to determine its role in class I-mediated organization of the actin cytoskeleton, cell survival, and cell proliferation in primary cultures of human aortic EC. Knockdown of FAK appreciably inhibited class I-mediated phosphorylation of Src at Tyr(418), p85 PI3K, and Akt at both Thr(308) and Ser(473) sites. FAK knockdown also reduced class I-mediated phosphorylation of paxillin at Try(118) and blocked class I-induced paxillin assembly into focal contacts. FAK small interfering RNA completely abrogated class I-mediated formation of actin stress fibers. Interestingly, FAK knockdown did not modify fibroblast growth factor receptor expression induced by class I ligation. However, FAK knockdown blocked HLA class I-stimulated cell cycle proliferation in the presence and absence of basic fibroblast growth factor. This study shows that FAK plays a critical role in class I-induced cell proliferation, cell survival, and focal adhesion assembly in EC and may promote the development of transplant-associated vasculopathy.
Yi-Ping Jin; Yael Korin; Xiaohai Zhang; Peter T Jindra; Enrique Rozengurt; Elaine F Reed
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  178     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-05     Completed Date:  2007-08-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7911-22     Citation Subset:  AIM; IM    
Department of Pathology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism
Actins / metabolism
Cell Proliferation
Cell Survival
Endothelium, Vascular / cytology,  enzymology,  immunology*
Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors,  genetics,  physiology*
Focal Adhesions* / drug effects,  genetics
Histocompatibility Antigens Class I / immunology*
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
RNA, Small Interfering / pharmacology
Receptors, Fibroblast Growth Factor / metabolism
src-Family Kinases / metabolism
Grant Support
Reg. No./Substance:
0/Actins; 0/Histocompatibility Antigens Class I; 0/RNA, Small Interfering; 0/Receptors, Fibroblast Growth Factor; EC 3-Kinase; EC Adhesion Protein-Tyrosine Kinases; EC Kinases; EC Proteins c-akt

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