Mothers against dpp participates in a DPP/TGF-β responsive serine-threonine kinase signal transduction cascade

Stuart J. Newfeld, Arun Mehra, Matthew A. Singer, Jeffrey L. Wrana, Liliana Attisano, William M. Gelbart

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Mothers against dpp (Mad) is the prototype of a family of genes required for signaling by TGF-β related ligands. In Drosophila, Mad is specifically required in cells responding to Decapentaplegic (DPP) signals. We further specify the role of Mad in DPP-mediated signaling by utilizing tkv(Q199D), an activated form of the DPP type I receptor serine-threonine kinase thick veins (tkv). In the embryonic midgut, tkv(Q199D) mimics DPP-mediated inductive interactions. Homozygous Mad mutations block signaling by tkv(Q199D). Appropriate responses to signaling by tkv(Q199D) are restored by expression of MAD protein in DPP-target cells. Endogenous MAD is phosphorylated in a ligand-dependent manner in Drosophila cell culture. DPP overexpression in the embryonic midgut induces MAD nuclear accumulation; after withdrawal of the overexpressed DPP signal, MAD is detected only in the cytoplasm. However, in three different tissues and developmental stages actively responding to endogenous DPP, MAD protein is detected in the cytoplasm but not in the nucleus. From these observations, we discuss possible roles for MAD in a DPP-dependent serine-threonine kinase signal transduction cascade integral to the proper interpretation of DPP signals.

Original languageEnglish (US)
Pages (from-to)3167-3176
Number of pages10
JournalDevelopment
Volume124
Issue number16
StatePublished - Sep 25 1997
Externally publishedYes

Keywords

  • DPP signal transduction
  • Drosophila melanogaster
  • Mad
  • Midgut morphogenesis
  • Nuclear accumulation
  • TGF-β family

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Newfeld, S. J., Mehra, A., Singer, M. A., Wrana, J. L., Attisano, L., & Gelbart, W. M. (1997). Mothers against dpp participates in a DPP/TGF-β responsive serine-threonine kinase signal transduction cascade. Development, 124(16), 3167-3176.