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XB-ART-18637
Proc Natl Acad Sci U S A January 23, 1996; 93 (2): 834-8.

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

Xu RH , Dong Z , Maeno M , Kim J , Suzuki A , Ueno N , Sredni D , Colburn NH , Kung HF .


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.

PubMed ID: 8570644
PMC ID: PMC40143
Article link: Proc Natl Acad Sci U S A


Species referenced: Xenopus
Genes referenced: bmp4 jun raf1


Article Images: [+] show captions
References [+] :
Alani, The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells. 1991, Pubmed