Mammalian dwarfins are phosphorylated in response to transforming growth factor β and are implicated in control of cell growth

Jonathan M. Yingling, Pradeep Das, Cathy Savage, Ming Zhang, Richard W. Padgett, Xiao Fan Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

The dwarfin protein family has been genetically implicated in transforming growth factor β (TGF-β)like signaling pathways in Drosophila and Caenorhabditis elegans. To investigate the role of these proteins in mammalian signaling pathways, we have isolated and studied two murine dwarfins, dwarfin-A and dwarfin-C. Using antibodies against dwarfin-A and dwarfin-C, we show that these two dwarfins and an immunogenically related protein, presumably also a dwarfin, are phosphorylated in a time- and dose- dependent manner in response to TGF-β. Bone morphogenetic protein 2, a TGF- β superfamily ligand, induces phosphorylation of only the related dwarfin protein. Thus, TGF-β superfamily members may use overlapping yet distinct dwarfins to mediate their intracellular signals. Furthermore, transient overexpression of either dwarfin-A or dwarfin-C causes growth arrest, implicating the dwarfins in growth regulation. This work provides strong biochemical and preliminary functional evidence that dwarfin-A and dwarfin-C represent prototypic members of a family of mammalian proteins that may serve as mediators of signaling pathways for TGF-β superfamily members.

Original languageEnglish (US)
Pages (from-to)8940-8944
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number17
DOIs
StatePublished - Aug 20 1996

ASJC Scopus subject areas

  • General

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