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

J. Biol. Chem., Vol. 282, Issue 49, 35679-35686, December 7, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/49/35679    most recent M707538200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sakaguchi, M. Articles by Huh, N.-h. Search for Related Content PubMed PubMed Citation Articles by Sakaguchi, M. Articles by Huh, N.-h. Social Bookmarking                      What's this?

Truncation of Annexin A1 Is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with Cytosolic Phospholipase A₂ in Normal and Malignant Squamous Epithelial Cells^*

Masakiyo Sakaguchi, Hitoshi Murata, Hiroyuki Sonegawa, Yoshihiko Sakaguchi^¶, Jun-ichiro Futami, Midori Kitazoe, Hidenori Yamada, and Nam-ho Huh¹

From the Department of Cell Biology and ^¶Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-chou, Okayama 700-8558 and the Department of Bioscience and Biotechnology, Okayama University Graduate School of Natural Science and Technology, Tsushimanaka, Okayama 700-8530, Japan

Regulation of cell growth and apoptosis is one of the pleiotropic functions of annexin A1 (ANXA1). Although previous reports on the overexpression of ANXA1 in many human cancers and on growth suppression and/or induction of apoptosis by ANXA1 may indicate the tumor-suppressive nature of ANXA1, molecular mechanisms of the function of ANXA1 remain largely unknown. Here we provide evidence that ANXA1 mechanistically links the epidermal growth factor-triggered growth signal pathway with cytosolic phospholipase A₂ (cPLA₂), an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 in normal human keratinocytes (NHK). Ca²⁺-dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA₂, resulting in inhibition of cPLA₂ activity, which is essential for the growth of NHK. On exposure of NHK to epidermal growth factor, ANXA1 was cleaved solely at Trp¹², and this cleavage was executed by cathepsin D. In squamous cancer cells, this pathway was shown to be constitutively activated. The newly found mechanistic intersection may be a promising target for establishing new measures against human cancer and other cell growth disorders.

Received for publication, September 10, 2007 , and in revised form, October 10, 2007.

^* 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. S1–S7.

¹ To whom correspondence should be addressed. Tel.: 81-86-235-7393; Fax: 81-86-235-7400; E-mail: namu{at}md.okayama-u.ac.jp.

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