PMID- 22784633 OWN - NLM STAT- MEDLINE DCOM- 20121113 LR - 20220224 IS - 1432-0436 (Electronic) IS - 0301-4681 (Print) IS - 0301-4681 (Linking) VI - 84 IP - 2 DP - 2012 Sep TI - A uniform human Wnt expression library reveals a shared secretory pathway and unique signaling activities. PG - 203-13 LID - 10.1016/j.diff.2012.06.004 [doi] AB - Wnt ligands are secreted morphogens that control multiple developmental processes during embryogenesis and adult homeostasis. A diverse set of receptors and signals have been linked to individual Wnts, but the lack of tools for comparative analysis has limited the ability to determine which of these signals are general for the entire Wnt family, and which define subsets of differently acting ligands. We have created a versatile Gateway library of clones for all 19 human Wnts. An analysis comparing epitope-tagged and untagged versions of each ligand shows that despite their similar expression at the mRNA level, Wnts exhibit considerable variation in stability, processing and secretion. At least 14 out of the 19 Wnts activate beta-catenin-dependent signaling, an activity that is cell type-dependent and tracks with the stabilization of beta-catenin and LRP6 phosphorylation. We find that the core Wnt modification and secretion proteins Porcupine (PORCN) and Wntless (WLS) are essential for all Wnts to signal through beta-catenin-dependent and independent pathways. This comprehensive toolkit provides critical tools and new insights into human Wnt gene expression and function. CI - Copyright (c) 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved. FAU - Najdi, Rani AU - Najdi R AD - Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA. FAU - Proffitt, Kyle AU - Proffitt K FAU - Sprowl, Stephanie AU - Sprowl S FAU - Kaur, Simran AU - Kaur S FAU - Yu, Jia AU - Yu J FAU - Covey, Tracy M AU - Covey TM FAU - Virshup, David M AU - Virshup DM FAU - Waterman, Marian L AU - Waterman ML LA - eng GR - R01 CA108697/CA/NCI NIH HHS/United States GR - CA108697/CA/NCI NIH HHS/United States GR - P30 CA062203/CA/NCI NIH HHS/United States GR - R01 CA096878/CA/NCI NIH HHS/United States GR - CA096878/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120709 PL - England TA - Differentiation JT - Differentiation; research in biological diversity JID - 0401650 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (LRP6 protein, human) RN - 0 (Low Density Lipoprotein Receptor-Related Protein-6) RN - 0 (Membrane Proteins) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (WLS protein, human) RN - 0 (Wnt Proteins) RN - 0 (beta Catenin) RN - EC 2.3.- (Acyltransferases) RN - EC 2.3.1.- (PORCN protein, human) SB - IM MH - 3T3 Cells MH - Acyltransferases MH - Animals MH - Gene Expression Profiling MH - *Gene Library MH - HEK293 Cells MH - Humans MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Low Density Lipoprotein Receptor-Related Protein-6/metabolism MH - Membrane Proteins/metabolism MH - Mice MH - Receptors, G-Protein-Coupled/metabolism MH - *Secretory Pathway MH - Wnt Proteins/genetics/*metabolism MH - *Wnt Signaling Pathway MH - beta Catenin/*metabolism PMC - PMC4015730 MID - NIHMS571720 EDAT- 2012/07/13 06:00 MHDA- 2012/11/14 06:00 PMCR- 2014/05/09 CRDT- 2012/07/13 06:00 PHST- 2012/04/24 00:00 [received] PHST- 2012/06/16 00:00 [accepted] PHST- 2012/07/13 06:00 [entrez] PHST- 2012/07/13 06:00 [pubmed] PHST- 2012/11/14 06:00 [medline] PHST- 2014/05/09 00:00 [pmc-release] AID - S0301-4681(12)00087-4 [pii] AID - 10.1016/j.diff.2012.06.004 [doi] PST - ppublish SO - Differentiation. 2012 Sep;84(2):203-13. doi: 10.1016/j.diff.2012.06.004. Epub 2012 Jul 9.