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

J. Biol. Chem., Vol. 281, Issue 17, 11872-11878, April 28, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/17/11872    most recent M511706200v1 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, H. Y. Articles by Jou, I. Search for Related Content PubMed PubMed Citation Articles by Kim, H. Y. Articles by Jou, I. Social Bookmarking                      What's this?

Raft-mediated Src Homology 2 Domain-containing Proteintyrosine Phosphatase 2 (SHP-2) Regulation in Microglia^*

From the Department of Pharmacology and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 442-721, Korea

Janus kinase-signal transducer and activator of transcription (JAK-STAT) signals play important roles in cell proliferation, apoptosis, and inflammation, and they recently have been considered as therapeutic targets for suppressing oncogenesis and inflammatory process. Phosphatases including Src homology 2 domain-containing protein-tyrosine phosphatases (SHPs), are well known as negative regulators of the JAK-STAT pathway, but their precise mechanisms are largely unknown. Based on our previous finding that in cultured rat brain microglia, gangliosides induce rapid and transient activation of the JAK-STAT pathway, we hypothesized that raft-mediated SHP-2 activation is involved in transient activation of JAK-STAT signaling by gangliosides. We first used Western blot analysis to confirm that gangliosides rapidly induce the phosphorylation of SHP-2. This was inhibited by pretreatment with the lipid raft disrupter filipin and was restored following filipin removal. Immunostaining using antibodies directed against p-SHP-2 and flotillin-1 revealed ganglioside-induced clustering and polarization of p-SHP-2 in membrane rafts. Raft-associated regulation of SHP-2 was further demonstrated in fractionation experiments using detergent and detergent-free sucrose gradient ultracentrifugation. Rapid SHP-2 recruitment to detergent-insoluble raft fractions by gangliosides was inhibited by filipin, further indicating the involvement of rafts. We also confirmed by immunoprecipitation that SHP-2 rapidly binds in a raft-dependent manner to JAK2 in response to gangliosides. Our study therefore showed that transient activation of the JAK-STAT pathway by gangliosides is accomplished by SHP-2 in a raft-dependent manner in brain microglia.

Received for publication, October 31, 2005 , and in revised form, February 2, 2006.

^* This work was supported by the Korea Science and Engineering Foundation through Chronic Inflammatory Disease Research Center Ajou University Grant R13-2003-019 (to I. Jou). 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 To whom correspondence should be addressed. Tel.: 82-31-219-5061; Fax: 82-31-219-5069; E-mail: jouilo{at}ajou.ac.kr.

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

This article has been cited by other articles:

				D.-A. Persaud-Sawin, S. Lightcap, and G. J. Harry Isolation of rafts from mouse brain tissue by a detergent-free method J. Lipid Res., April 1, 2009; 50(4): 759 - 767. [Abstract] [Full Text] [PDF]