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

I. Chun Tsai, Jeffrey D. Amack, Zhong Hua Gao, Vimla Band, H. Joseph Yost, David M. Virshup

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIε) is a Wnt-regulated kinase that regulates Wnt/β-catenin signaling and has a β-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIε binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIε phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIε, enhances the CKIε-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 CKIε also transduces Wnt/β-catenin signaling, inhibition of Rap1 does not alter β-catenin-regulated gene expression. Our data demonstrate a role for CKIε in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIε-mediated control of Rap1 signaling.

Original languageEnglish (US)
Pages (from-to)335-347
Number of pages13
JournalDevelopmental Cell
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Casein Kinase I
GTPase-Activating Proteins
Gastrulation
Catenins
Morphogenesis
Phosphorylation
Monomeric GTP-Binding Proteins
Zebrafish
Xenopus
Caseins
Gene expression
Vertebrates
Phosphotransferases
Chemical activation
Gene Expression
Degradation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Tsai, I. Chun ; Amack, Jeffrey D. ; Gao, Zhong Hua ; Band, Vimla ; Yost, H. Joseph ; Virshup, David M. / A Wnt-CKIε-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein. In: Developmental Cell. 2007 ; Vol. 12, No. 3. pp. 335-347.
@article{67b151203ec440429e001d774ec87d65,
title = "A Wnt-CKIε-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein",
abstract = "Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIε) is a Wnt-regulated kinase that regulates Wnt/β-catenin signaling and has a β-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIε binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIε phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIε, enhances the CKIε-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 CKIε also transduces Wnt/β-catenin signaling, inhibition of Rap1 does not alter β-catenin-regulated gene expression. Our data demonstrate a role for CKIε in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIε-mediated control of Rap1 signaling.",
author = "Tsai, {I. Chun} and Amack, {Jeffrey D.} and Gao, {Zhong Hua} and Vimla Band and Yost, {H. Joseph} and Virshup, {David M.}",
year = "2007",
month = "3",
day = "1",
doi = "10.1016/j.devcel.2007.02.009",
language = "English (US)",
volume = "12",
pages = "335--347",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "3",

}

A Wnt-CKIε-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein. / Tsai, I. Chun; Amack, Jeffrey D.; Gao, Zhong Hua; Band, Vimla; Yost, H. Joseph; Virshup, David M.

In: Developmental Cell, Vol. 12, No. 3, 01.03.2007, p. 335-347.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Wnt-CKIε-Rap1 Pathway Regulates Gastrulation by Modulating SIPA1L1, a Rap GTPase Activating Protein

AU - Tsai, I. Chun

AU - Amack, Jeffrey D.

AU - Gao, Zhong Hua

AU - Band, Vimla

AU - Yost, H. Joseph

AU - Virshup, David M.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIε) is a Wnt-regulated kinase that regulates Wnt/β-catenin signaling and has a β-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIε binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIε phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIε, enhances the CKIε-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 CKIε also transduces Wnt/β-catenin signaling, inhibition of Rap1 does not alter β-catenin-regulated gene expression. Our data demonstrate a role for CKIε in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIε-mediated control of Rap1 signaling.

AB - Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIε) is a Wnt-regulated kinase that regulates Wnt/β-catenin signaling and has a β-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIε binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIε phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIε, enhances the CKIε-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 CKIε also transduces Wnt/β-catenin signaling, inhibition of Rap1 does not alter β-catenin-regulated gene expression. Our data demonstrate a role for CKIε in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIε-mediated control of Rap1 signaling.

UR - http://www.scopus.com/inward/record.url?scp=33847231810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847231810&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2007.02.009

DO - 10.1016/j.devcel.2007.02.009

M3 - Article

C2 - 17336901

AN - SCOPUS:33847231810

VL - 12

SP - 335

EP - 347

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 3

ER -