R-smad competition controls activin receptor output in drosophila

Aidan J. Peterson, Philip A. Jensen, Mary Jane Shimell, Ray Stefancsik, Ranjula Wijayatonge, Rachel Herder, Laurel A. Raftery, Michael B. O'Connor

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Animals use TGF-β superfamily signal transduction pathways during development and tissue maintenance. The superfamily has traditionally been divided into TGF-β/Activin and BMP branches based on relationships between ligands, receptors, and R-Smads. Several previous reports have shown that, in cell culture systems, "BMP-specific" Smads can be phosphorylated in response to TGF-β/Activin pathway activation. Using Drosophila cell culture as well as in vivo assays, we find that Baboon, the Drosophila TGF-β/Activin-specific Type I receptor, can phosphorylate Mad, the BMP-specific R-Smad, in addition to its normal substrate, dSmad2. The Baboon-Mad activation appears direct because it occurs in the absence of canonical BMP Type I receptors. Wing phenotypes generated by Baboon gain-of-function require Mad, and are partially suppressed by over-expression of dSmad2. In the larval wing disc, activated Baboon cell-autonomously causes C-terminal Mad phosphorylation, but only when endogenous dSmad2 protein is depleted. The Baboon-Mad relationship is thus controlled by dSmad2 levels. Elevated P-Mad is seen in several tissues of dSmad2 protein-null mutant larvae, and these levels are normalized in dSmad2; baboon double mutants, indicating that the cross-talk reaction and Smad competition occur with endogenous levels of signaling components in vivo. In addition, we find that high levels of Activin signaling cause substantial turnover in dSmad2 protein, providing a potential cross-pathway signal-switching mechanism. We propose that the dual activity of TGF-β/Activin receptors is an ancient feature, and we discuss several ways this activity can modulate TGF-β signaling output.

Original languageEnglish (US)
Article numbere36548
JournalPloS one
Volume7
Issue number5
DOIs
StatePublished - May 1 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Peterson, A. J., Jensen, P. A., Shimell, M. J., Stefancsik, R., Wijayatonge, R., Herder, R., Raftery, L. A., & O'Connor, M. B. (2012). R-smad competition controls activin receptor output in drosophila. PloS one, 7(5), [e36548]. https://doi.org/10.1371/journal.pone.0036548