title: Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.
abstract: 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.
authors.affiliation: Department of Pharmacology, Duke University, Durham, NC 27710, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Yingling
authors.forename: P
authors.initials: P
authors.lastname: Das
authors.forename: C
authors.initials: C
authors.lastname: Savage
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: R W
authors.initials: RW
authors.lastname: Padgett
authors.forename: X F
authors.initials: XF
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D010766:Phosphorylation; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051785:Smad Proteins; D051902:Smad5 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D051785:Smad Proteins; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; C497799:Smad5 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta