title: POSH misexpression induces caspase-dependent cell death in Drosophila.
abstract: POSH (Plenty of SH3 domains) is a scaffold for signaling proteins regulating cell survival. Specifically, POSH promotes assembly of a complex including Rac GTPase, mixed lineage kinase (MLK), MKK7, and Jun kinase (JNK). In Drosophila, genetic analysis implicated POSH in Tak1-dependent innate immune response, in part through regulation of JNK signaling. Homologs of the POSH signaling complex components, MLK and MKK7, are essential in Drosophila embryonic dorsal closure. Using a gain-of-function approach, we tested whether POSH plays a role in this process. Ectopic expression of POSH in the embryo causes dorsal closure defects due to apoptosis of the amnioserosa, but ectodermal JNK signaling is normal. Phenotypic consequences of POSH expression were found to be dependent on Drosophila Nc, the caspase-9 homolog, but only partially on Tak1 and not at all on Slpr and Hep. These results suggest that POSH may use different signaling complexes to promote cell death in distinct contexts.
authors.affiliation: Department of Biological Sciences, 202 Life Sciences Annex, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Lennox
authors.forename: Beth
authors.initials: B
authors.lastname: Stronach
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009419:Nerve Tissue Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C453299:POSH protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; C118731:dronc protein, Drosophila