Cited by 67Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationProtein Kinase Regulation and GTPase Signaling

A Wnt-CKIɛ-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein

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Tsai, I-Chun, Amack, Jeffrey D., Gao, Zhong-Hua, Band, Vimla, Yost, H. Joseph, Virshup, David M.·2007·Developmental Cell

Abstract

Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIvarepsilon) is a Wnt-regulated kinase that regulates Wnt/beta-catenin signaling and has a beta-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIvarepsilon binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIvarepsilon phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIvarepsilon, enhances the CKIvarepsilon-dependent phosphorylation and degradation of SIPA1L1. In early Xenopus or zebrafish development, inactivation of the Rap1 pathway results in abnormal gastrulation and a shortened anterior-posterior axis. Although CKIvarepsilon also transduces Wnt/beta-catenin signaling, inhibition of Rap1 does not alter beta-catenin-regulated gene expression. Our data demonstrate a role for CKIvarepsilon in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIvarepsilon-mediated control of Rap1 signaling.

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Crossref · 10.1016/j.devcel.2007.02.009

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  • During gastrulation, Wnt signaling via casein kinase inhibits the Rap1-GTPase leading to cytoskeletal modulation.

    “During gastrulation, Wnt signaling via casein kinase inhibits the Rap1-GTPase leading to cytoskeletal modulation.106,107”

    From Wnt signal transduction pathways (2008) · cites this paper as [107]

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Authors
Tsai, I.-C., Amack, J. D., Gao, Z.-H., Band, V., Yost, H. J., & Virshup, D. M.
Affiliations
  • University of Utah (US)
  • Northwestern University (US)
Corresponding author
Virshup, David M.
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2007-03
Volume
12
Issue
3
Pages
335-347
ISSN
1534-5807 (ISSN-L)
OpenAlex
W1984363659
Cited by
67
References
55
Citations by year
2024: 4 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 5
FWCI
3.31
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (P01 CA73992, P30 CA42014, R01 HL057840)
  • Huntsman Cancer Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
non-canonical Wnt signaling, casein kinase I epsilon, Rap1, GTPase-activating protein, gastrulation, protein phosphorylation, protein stability, anterior-posterior axis, morphogenesis, Xenopus, zebrafish, β-catenin-independent signaling
MeSH terms
Animals, Cell Line, Enzyme Activation, Gastrula, Humans, Phosphorylation, Xenopus, Zebrafish, Signal Transduction, Gene Expression Regulation, Developmental, Body Patterning, GTPase-Activating Proteins, rap1 GTP-Binding Proteins, Xenopus Proteins, Zebrafish Proteins, Embryonic Development, Casein Kinase 1 epsilon, Wnt Proteins, beta Catenin

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