A Wnt-CKIɛ-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein
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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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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)
- PMC
- PMC1857327
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2366 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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