Involvement of Ras/Raf/AP-1 in BMP-4 signaling during Xenopus embryonic development

Ren He Xu, Zigang Dong, Mitsugu Maeno, Jaebong Kim, Atsushi Suzuki, Naoto Ueno, Dvora Sredni, Nancy H. Colburn, Hsiang Fu Kung

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61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)834-838
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number2
DOIs
StatePublished - Jan 23 1996

Keywords

  • activator protein 1
  • bone morphogenetic protein 4

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