HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, Y.-P. Articles by Reed, E. F. Search for Related Content PubMed PubMed Citation Articles by Jin, Y.-P. Articles by Reed, E. F.

RNA Interference Elucidates the Role of Focal Adhesion Kinase in HLA Class I-Mediated Focal Adhesion Complex Formation and Proliferation in Human Endothelial Cells¹

Yi-Ping Jin^*, Yael Korin^*, Xiaohai Zhang^*, Peter T. Jindra^*, Enrique Rozengurt and Elaine F. Reed^2,*

^* Department of Pathology and Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095

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 Tyr⁴¹⁸, p85 PI3K, and Akt at both Thr³⁰⁸ and Ser⁴⁷³ sites. FAK knockdown also reduced class I-mediated phosphorylation of paxillin at Try¹¹⁸ 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institute of Allergy and Infectious Diseases Grant R01 AI 42819 and the American Heart Association Grant-in-Aid 9750894A.

² Address correspondence and reprint requests to Dr. Elaine F. Reed, Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, 1000 Veteran Avenue, Los Angeles, CA 90095. E-mail address: ereed{at}mednet.ucla.edu

³ Abbreviations used in this paper: TAV, transplant-associated vasculopathy; bFGF, basic fibroblast growth factor; EC, endothelial cell; FAK, focal adhesion kinase; FGF, fibroblast growth factor; FGFR, FGF receptor; SH, Src homology; siRNA, small interfering RNA; PYK2, proline-rich tyrosine kinase 2.

This article has been cited by other articles:

				P. T. Jindra, Y.-P. Jin, E. Rozengurt, and E. F. Reed HLA Class I Antibody-Mediated Endothelial Cell Proliferation via the mTOR Pathway J. Immunol., February 15, 2008; 180(4): 2357 - 2366. [Abstract] [Full Text] [PDF]