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

J. Biol. Chem., Vol. 283, Issue 32, 22076-22088, August 8, 2008

This Article Full Text Full Text (PDF) Author Profile Supplemental Data All Versions of this Article: 283/32/22076    most recent M803901200v1 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 Buglino, J. A. Articles by Resh, M. D. Search for Related Content PubMed PubMed Citation Articles by Buglino, J. A. Articles by Resh, M. D. Related Collections Papers Of The Week Social Bookmarking                      What's this?

Hhat Is a Palmitoylacyltransferase with Specificity for N-Palmitoylation of Sonic Hedgehog^*

From the Cell Biology Program, Memorial Sloan-Kettering Cancer Center, and the Graduate Program in Biochemistry, Cell and Molecular Biology, Weill Graduate School of Medical Sciences, Cornell University, New York, New York 10065

Palmitoylation of Sonic Hedgehog (Shh) is critical for effective long- and short-range signaling. Genetic screens uncovered a potential palmitoylacyltransferase (PAT) for Shh, Hhat, but the molecular mechanism of Shh palmitoylation remains unclear. Here, we have developed and exploited an in vitro Shh palmitoylation assay to purify Hhat to homogeneity. We provide direct biochemical evidence that Hhat is a PAT with specificity for attaching palmitate via amide linkage to the N-terminal cysteine of Shh. Other palmitoylated proteins (e.g. PSD95 and Wnt) are not substrates for Hhat, and Porcupine, a putative Wnt PAT, does not palmitoylate Shh. Neither autocleavage nor cholesterol modification is required for Shh palmitoylation. Both the Shh precursor and mature protein are N-palmitoylated by Hhat, and the reaction occurs during passage through the secretory pathway. This study establishes Hhat as a bona fide Shh PAT and serves as a model for understanding how secreted morphogens are modified by distinct PATs.

Received for publication, May 21, 2008 , and in revised form, June 4, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants GM57966 and GM008539. 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 "Experimental Procedures."

This article was selected as a Paper of the Week.

¹ To whom correspondence should be addressed: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 143, New York, NY 10065. Tel.: 212-639-2514; Fax: 212-717-3317; E-mail: m-resh{at}ski.mskcc.org.

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

This article has been cited by other articles:

				B. C. Jennings, M. J. Nadolski, Y. Ling, M. B. Baker, M. L. Harrison, R. J. Deschenes, and M. E. Linder 2-Bromopalmitate and 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one inhibit DHHC-mediated palmitoylation in vitro J. Lipid Res., February 1, 2009; 50(2): 233 - 242. [Abstract] [Full Text] [PDF]

				M. Varjosalo and J. Taipale Hedgehog: functions and mechanisms Genes & Dev., September 15, 2008; 22(18): 2454 - 2472. [Abstract] [Full Text] [PDF]