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

J. Biol. Chem., Vol. 282, Issue 28, 20475-20483, July 13, 2007

This Article Full Text Full Text (PDF) An addition or correction has been published All Versions of this Article: 282/28/20475    most recent M702610200v1 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 van Kerkhof, P. Articles by Strous, G. J. Search for Related Content PubMed PubMed Citation Articles by van Kerkhof, P. Articles by Strous, G. J. Social Bookmarking                      What's this?

The Ubiquitin Ligase SCF(TrCP) Regulates the Degradation of the Growth Hormone Receptor^*

From the Department of Cell Biology, University Medical Center Utrecht and Institute of Biomembranes, Heidelberglaan 100, AZU-G02.525, 3584 CX Utrecht, The Netherlands

SCF ubiquitin ligases play a pivotal role in the regulation of cell division and various signal transduction pathways, which in turn are involved in cell growth, survival, and transformation. SCF(TrCP) recognizes the double phosphorylated DSGXS destruction motif in -catenin and IB. We show that the same ligase drives endocytosis and degradation of the growth hormone receptor (GHR) in a ligand-independent fashion. The F-box protein -TrCP binds directly and specifically with its WD40 domain to a novel recognition motif, previously designated as the ubiquitin-dependent endocytosis motif. Receptor degradation requires an active neddylation system, implicating ubiquitin ligase activity. GHR-TrCP binding, but not GHR ubiquitination, is necessary for endocytosis. TrCP2 silencing is more effective on GHR degradation and endocytosis than TrCP1, although overexpression of either isoform restores TrCP function in silenced cells. Together, these findings provide direct evidence for a key role of the SCF(TrCP) in the endocytosis and degradation of an important factor in growth, immunity, and life span regulation.

Received for publication, March 27, 2007 , and in revised form, May 10, 2007.

^* This work was supported by Netherlands Organization for Scientific Research Grant NWO-ALW 814-02-011. 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: Dept. of Cell Biology, University Medical Center Utrecht and Institute of Biomembranes, Heidelberglaan 100, AZU-G02.525, 3584 CX Utrecht, The Netherlands. Tel.: 31-30-250-6476; Fax: 31-30-254-1797; E-mail: gstrous{at}umcutrecht.nl.

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

This article has been cited by other articles:

				X. Tan and N. Zheng Hormone signaling through protein destruction: a lesson from plants Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E223 - E227. [Abstract] [Full Text] [PDF]

				B. Varghese, H. Barriere, C. J. Carbone, A. Banerjee, G. Swaminathan, A. Plotnikov, P. Xu, J. Peng, V. Goffin, G. L. Lukacs, et al. Polyubiquitination of Prolactin Receptor Stimulates Its Internalization, Postinternalization Sorting, and Degradation via the Lysosomal Pathway Mol. Cell. Biol., September 1, 2008; 28(17): 5275 - 5287. [Abstract] [Full Text] [PDF]