Interaction of Drosophila Inhibitors of Apoptosis with Thick Veins, a Type I Serine/Threonine Kinase Receptor for Decapentaplegic*

Decapentaplegic (Dpp) is a Drosophilamember of bone morphogenetic proteins, which belong to the transforming growth factor-β superfamily. Members of this family regulate a variety of biological processes such as cell proliferation, morphogenesis, immune response, and apoptosis. Dpp plays a critical role in many aspects of Drosophila development. Members of the transforming growth factor-β superfamily bind to two different types of serine/threonine kinase receptors, termed type I and type II. Type I receptors act as downstream components of type II receptors in the receptor complexes. Therefore, intracellular proteins that interact with the type I receptors are likely to play important roles in signaling. Several proteins have been identified through protein-protein interaction screenings. We identifiedDrosophila inhibitor of apoptosis (DIAP) 1 as an interacting protein of a Dpp type I receptor, Thick veins (Tkv). DIAP1 associates with Tkv in vivo. The binding region in DIAP1 is mapped to its C-terminal RING finger region. DIAP2, anotherDrosophila member of the inhibitor of apoptosis protein family, also interacts with Tkv in vivo. These data suggest that DIAP1 and DIAP2 may be involved, possibly as negative regulators, in the Dpp signaling pathway, which leads to cell apoptosis.

[1]  Kohei Miyazono,et al.  TGF-β signalling from cell membrane to nucleus through SMAD proteins , 1997, Nature.

[2]  W. Vale,et al.  Smad8 mediates the signaling of the receptor serine kinase , 1997 .

[3]  A. Harvey,et al.  Inhibition of reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs). , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. H. Chen,et al.  Involvement of caspase family proteases in transforming growth factor-beta-induced apoptosis. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[5]  J. Massagué,et al.  Mechanism of TGFβ receptor inhibition by FKBP12 , 1997, The EMBO journal.

[6]  A. Harvey,et al.  Doom, a product of the Drosophila mod(mdg4) gene, induces apoptosis and binds to baculovirus inhibitor-of-apoptosis proteins , 1997, Molecular and cellular biology.

[7]  R. W. Padgett,et al.  Genetic and biochemical analysis of TGFβ signal transduction , 1997 .

[8]  D. Vaux,et al.  Inhibition of interleukin 1 beta-converting enzyme-mediated apoptosis of mammalian cells by baculovirus IAP. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. Goeddel,et al.  The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Charng,et al.  FKBP-12 Recognition Is Dispensable For Signal Generation by Type I Transforming Growth Factor-β Receptors* , 1996, The Journal of Biological Chemistry.

[11]  K. Miyazono,et al.  Characterization of the Interaction of FKBP12 with the Transforming Growth Factor-β Type I Receptor in Vivo* , 1996, The Journal of Biological Chemistry.

[12]  P. Donahoe,et al.  The Immunophilin FKBP12 Functions as a Common Inhibitor of the TGFβ Family Type I Receptors , 1996, Cell.

[13]  B. Hogan,et al.  Bone morphogenetic proteins: multifunctional regulators of vertebrate development. , 1996, Genes & development.

[14]  T. Lecuit,et al.  Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye. , 1996, Development.

[15]  J. Massagué,et al.  Interaction of Transforming Growth Factor-β Receptor I with Farnesyl-protein Transferase-α in Yeast and Mammalian Cells* , 1996, The Journal of Biological Chemistry.

[16]  C. Thompson,et al.  A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. , 1996, The EMBO journal.

[17]  D. Vaux,et al.  Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[18]  L. Niswander,et al.  Requirement for BMP Signaling in Interdigital Apoptosis and Scale Formation , 1996, Science.

[19]  Patricia K. Donahoe,et al.  The p21RAS Farnesyltransferase α Subunit in TGF-β and Activin Signaling , 1996, Science.

[20]  K. Tamai,et al.  Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes , 1996, Nature.

[21]  R. W. Padgett,et al.  Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P. Howe,et al.  Interaction of transforming growth factor beta receptors with apolipoprotein J/clusterin. , 1996, Biochemistry.

[23]  Mike Rothe,et al.  The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins , 1995, Cell.

[24]  Gerald M. Rubin,et al.  Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death , 1995, Cell.

[25]  K. Miyazono,et al.  Interaction of the Transforming Growth Factor-β Type I Receptor with Farnesyl-protein Transferase-α (*) , 1995, The Journal of Biological Chemistry.

[26]  R. Derynck,et al.  A WD-domain protein that is associated with and phosphorylated by the type II TGF-β receptor , 1995, Nature.

[27]  J. Massagué,et al.  GS domain mutations that constitutively activate T beta R‐I, the downstream signaling component in the TGF‐beta receptor complex. , 1995, The EMBO journal.

[28]  M. Affolter,et al.  An absolute requirement for both the type II and type I receptors, punt and thick veins, for Dpp signaling in vivo , 1995, Cell.

[29]  W. Gelbart,et al.  Drosophila Dpp signaling is mediated by the punt gene product: A dual ligand-binding type II receptor of the TGFβ receptor family , 1995, Cell.

[30]  J. Sekelsky,et al.  Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. , 1995, Genetics.

[31]  W. Gelbart,et al.  Characterization and relationship of dpp receptors encoded by the saxophone and thick veins genes in Drosophila , 1994, Cell.

[32]  J. Massagué,et al.  Identification of two bone morphogenetic protein type I receptors in Drosophila and evidence that Brk25D is a decapentaplegic receptor , 1994, Cell.

[33]  P. Donahoe,et al.  Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12. , 1994, Science.

[34]  Markus Affolter,et al.  Receptor serine/threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic , 1994, Cell.

[35]  M. Birnbaum,et al.  An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs , 1994, Journal of virology.

[36]  R. W. Padgett,et al.  The Drosophila saxophone gene: a serine-threonine kinase receptor of the TGF-beta superfamily. , 1994, Science.

[37]  D. Kingsley,et al.  The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. , 1994, Genes & development.

[38]  Roger Brent,et al.  C dil, a Human Gl and S Phase Protein Phosphatase That Associates with Cdk2 , 2003 .

[39]  J. Massagué,et al.  Identification of a Drosophila activin receptor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[40]  R. J. Clem,et al.  An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif , 1993, Journal of virology.