PUBLICATION

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

Authors
Tsai, I.C., Amack, J.D., Gao, Z.H., Band, V., Yost, H.J., and Virshup, D.M.
ID
ZDB-PUB-070310-7
Date
2007
Source
Developmental Cell   12(3): 335-347 (Journal)
Registered Authors
Amack, Jeffrey, Yost, H. Joseph
Keywords
none
MeSH Terms
  • Animals
  • Body Patterning/physiology
  • Casein Kinase 1 epsilon/genetics
  • Casein Kinase 1 epsilon/metabolism*
  • Cell Line
  • Embryonic Development/physiology*
  • Enzyme Activation/physiology
  • GTPase-Activating Proteins/genetics
  • GTPase-Activating Proteins/metabolism*
  • Gastrula/cytology
  • Gastrula/metabolism*
  • Gene Expression Regulation, Developmental/genetics
  • Humans
  • Phosphorylation
  • Signal Transduction/genetics
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism*
  • Xenopus
  • Xenopus Proteins/genetics
  • Xenopus Proteins/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • beta Catenin/genetics
  • beta Catenin/metabolism
  • rap1 GTP-Binding Proteins/genetics
  • rap1 GTP-Binding Proteins/metabolism*
PubMed
17336901 Full text @ Dev. Cell
Abstract
Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIepsilon) 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 CKIepsilon phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIepsilon, enhances the CKIepsilon-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 CKIepsilon also transduces Wnt/beta-catenin signaling, inhibition of Rap1 does not alter beta-catenin-regulated gene expression. Our data demonstrate a role for CKIepsilon in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIepsilon-mediated control of Rap1 signaling.
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