Hhat is a palmitoylacyl transferase with specificity for N-palmitoylation of sonic hedgehog.
J Biol Chem. 2008 Jun 4;
Authors: Buglino JA, Resh MD
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 develop and exploit 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 (eg PSD95,Wnt) are not substrates for Hhat, and Porcupine, a putative Wnt PAT, does not palmitoylate Shh. Neither autocleavage nor cholesterol modification are 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. These studies establish Hhat as a bona fide Shh PAT and serve as a model for understanding how secreted morphogens are modified by distinct PATs.
PMID: 18534984 [PubMed - as supplied by publisher]
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PubMed: hedgehog
NCBI: db=PubMed; Term=hedgehog
