title: Identification of the WNT1 residues required for palmitoylation by Porcupine.
abstract: The post-translational palmitoylation of WNT morphogens is critical for proper signaling during embryogenesis and adult homeostasis. The addition of palmitoyl groups to WNT proteins is catalyzed by Porcupine (PORCN). However, the Wnt amino acid residues required for recognition and palmitoylation by PORCN have not been fully characterized. We show that WNT1 residues 214-234 are sufficient for PORCN-dependent palmitoylation of Ser224. Substitution of Ser224 with Thr, but not Cys, is tolerated in palmitoylation and biological assays. Our data highlight the importance of palmitoylation for WNT1 activity and establish PORCN as an O-acyl transferase for WNT1.
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
authors.forename: M
authors.initials: M
authors.lastname: Miranda
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Galli
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
authors.forename: M
authors.initials: M
authors.lastname: Enriquez
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Szabo
authors.affiliation: Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Hannoush
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA. Electronic address: LBurrus@sfsu.edu.
authors.forename: L W
authors.initials: LW
authors.lastname: Burrus
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019308:Palmitic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity; D051155:Wnt1 Protein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D051155:Wnt1 Protein; D019308:Palmitic Acid; D000217:Acyltransferases; C491188:PORCN protein, human
keywords: Chick; Membrane-bound O-acyl transferase; Palmitoylation; Porcupine; Spinal cord; WNT1