Involvement of Ras/Raf/AP-1 in BMP-4 Signaling During Xenopus Embryonic Development

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1996 Jan 23

PMID 8570644

Citations 13

Authors

R H Xu

Z Dong

M Maeno

J Kim

A Suzuki

N Ueno

D Sredni

N H Colburn

H F Kung

Affiliations

Soon will be listed here.

Abstract

Previously, we elucidated the role of bone morphogenetic protein 4 (BMP-4) in the dorsal-ventral patterning of the Xenopus embryo by using a dominant negative mutant of the BMP-4 receptor (DN-BR). The present paper describes the involvement of Ras, Raf, and activator protein 1 (AP-1) in BMP-4 signaling during Xenopus embryonic development. The AP-1 activity was determined by injecting an AP-1-dependent luciferase reporter gene into two-cell-stage Xenopus embryos and measuring the luciferase activity at various developmental stages. We found that injection of BMP-4 mRNA increased AP-1 activity, whereas injection of DN-BR mRNA inhibited AP-1 activity. Similar inhibitory effects were seen with injection of mRNAs encoding dominant negative mutants of c-Ha-Ras, c-Raf, or c-Jun. These results suggest that the endogenous AP-1 activity is regulated by BMP-4/Ras/Raf/Jun signals. We next investigated the effects of Ras/Raf/AP-1 signals on the biological functions of BMP-4. DN-BR-induced dorsalization of the embryo, revealed by the formation of a secondary body axis or dorsalization of the ventral mesoderm explant analyzed by histological and molecular criteria, was significantly reversed by coinjection of [Val12]Ha-Ras, c-Raf, or c-Jun mRNA. Furthermore, the BMP-4-stimulated erythroid differentiation in the ventral mesoderm was substantially inhibited by coinjection with the dominant negative c-Ha-Ras, c-Raf, or c-Jun mutant. Our results suggest the involvement of Ras/Raf/AP-1 in the BMP-4 signaling pathway.

Citing Articles

The role of heterodimeric AP-1 protein comprised of JunD and c-Fos proteins in hematopoiesis.

Lee S, Yoon J, Lee M, Jung S, Kim D, Bode A J Biol Chem. 2012; 287(37):31342-8.

PMID: 22822070 PMC: 3438963. DOI: 10.1074/jbc.M112.387266.

The function of heterodimeric AP-1 comprised of c-Jun and c-Fos in activin mediated Spemann organizer gene expression.

Lee S, Yoon J, Lee H, Hwang Y, Cha S, Jeong C PLoS One. 2011; 6(7):e21796.

PMID: 21829441 PMC: 3146467. DOI: 10.1371/journal.pone.0021796.

Histone XH2AX is required for Xenopus anterior neural development: critical role of threonine 16 phosphorylation.

Lee S, Lau A, Jeong C, Shim J, Kim H, Kim J J Biol Chem. 2010; 285(38):29525-34.

PMID: 20639511 PMC: 2937984. DOI: 10.1074/jbc.M110.127233.

Multiple signaling pathways converge to regulate bone-morphogenetic-protein-dependent glial gene expression.

Dore J, DeWitt J, Setty N, Donald M, Joo E, Chesarone M Dev Neurosci. 2009; 31(6):473-86.

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c-Jun N-terminal kinase 1 phosphorylates Myt1 to prevent UVA-induced skin cancer.

Choi H, Bode A, Shim J, Lee S, Dong Z Mol Cell Biol. 2009; 29(8):2168-80.

PMID: 19204086 PMC: 2663297. DOI: 10.1128/MCB.01508-08.

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