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

J. Biol. Chem., Vol. 283, Issue 1, 341-349, January 4, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/1/341    most recent M704180200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yun, S. Articles by Suh, P.-G. Search for Related Content PubMed PubMed Citation Articles by Yun, S. Articles by Suh, P.-G. Social Bookmarking                      What's this?

Phospholipase C- Augments Epidermal Growth Factor-dependent Cell Growth by Inhibiting Epidermal Growth Factor Receptor Down-regulation^*

Sanguk Yun, Won-Pyo Hong, Jang Hyun Choi, Kye Sook Yi, Suhn-Kee Chae, Sung Ho Ryu, and Pann-Ghill Suh¹

From the Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyung-Buk 790-784, Republic of Korea and the Department of Biochemistry and Biomed Research Center, Paichai University, Daejeon 302-735, Republic of Korea

The down-regulation of the epidermal growth factor (EGF) receptor is critical for the termination of EGF-dependent signaling, and the dysregulation of this process can lead to oncogenesis. In the present study, we suggest a novel mechanism for the regulation of EGF receptor down-regulation by phospholipase C-. The overexpression of PLC- led to an increase in receptor recycling and decreased the down-regulation of the EGF receptor in COS-7 cells. Adaptor protein complex 2 (AP2) was identified as a novel binding protein that associates with the PLC- RA2 domain independently of Ras. The interaction of PLC- with AP2 was responsible for the suppression of EGF receptor down-regulation, since a perturbation in this interaction abolished this effect. Enhanced EGF receptor stability by PLC- led to the potentiation of EGF-dependent growth in COS-7 cells. Finally, the knockdown of PLC- in mouse embryo fibroblast cells elicited a severe defect in EGF-dependent growth. Our results indicated that PLC- could promote EGF-dependent cell growth by suppressing receptor down-regulation.

Received for publication, May 21, 2007 , and in revised form, October 12, 2007.

^* This study was supported in part by the National R & D Program for Fusion Strategy of Advanced Technologies of the Ministry of Commerce, Industry, and Energy. This work was supported in part by National Research Laboratory of the Korea Science and Engineering Foundation Grant M10600000281-06J0000-28110 and the Brain Korea21 Program of the Ministry of Education of Korea. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1 and 2.

¹ To whom correspondence should be addressed. Tel.: 82-54-279-2293; Fax: 82-54-279-0645; E-mail: pgs{at}postech.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?