TY - JOUR
T1 - Mammalian dwarfins are phosphorylated in response to transforming growth factor β and are implicated in control of cell growth
AU - Yingling, Jonathan M.
AU - Das, Pradeep
AU - Savage, Cathy
AU - Zhang, Ming
AU - Padgett, Richard W.
AU - Wang, Xiao Fan
PY - 1996/8/20
Y1 - 1996/8/20
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.93.17.8940
DO - 10.1073/pnas.93.17.8940
M3 - Article
C2 - 8799132
SN - 0027-8424
VL - 93
SP - 8940
EP - 8944
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -