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
Citation
Tsai, I.C., Amack, J.D., Gao, Z.H., Band, V., Yost, H.J., and Virshup, D.M. (2007) A Wnt-CKIε-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein. Developmental Cell. 12(3):335-347.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping