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

Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8940-4. doi: 10.1073/pnas.93.17.8940.


The dwarfin protein family has been genetically implicated in transforming growth factor beta (TGF-beta)-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-beta. Bone morphogenetic protein 2, a TGF-beta superfamily ligand, induces phosphorylation of only the related dwarfin protein. Thus, TGF-beta 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-beta superfamily members.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Division / drug effects*
  • Cell Line
  • Cloning, Molecular
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Phosphoproteins*
  • Phosphorylation
  • Rats
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Smad Proteins
  • Smad5 Protein
  • Trans-Activators*
  • Transforming Growth Factor beta / pharmacology*


  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Phosphoproteins
  • Smad Proteins
  • Smad5 Protein
  • Smad5 protein, mouse
  • Smad5 protein, rat
  • Trans-Activators
  • Transforming Growth Factor beta

Associated data

  • GENBANK/U58992
  • GENBANK/U58993