title: Overlapping roles of Drosophila Drak and Rok kinases in epithelial tissue morphogenesis.
abstract: Dynamic regulation of cytoskeletal contractility through phosphorylation of the nonmuscle Myosin-II regulatory light chain (MRLC) provides an essential source of tension for shaping epithelial tissues. Rho GTPase and its effector kinase ROCK have been implicated in regulating MRLC phosphorylation in vivo, but evidence suggests that other mechanisms must be involved. Here, we report the identification of a single Drosophila homologue of the Death-associated protein kinase (DAPK) family, called Drak, as a regulator of MRLC phosphorylation. Based on analysis of null mutants, we find that Drak broadly promotes proper morphogenesis of epithelial tissues during development. Drak activity is largely redundant with that of the Drosophila ROCK orthologue, Rok, such that it is essential only when Rok levels are reduced. We demonstrate that these two kinases synergistically promote phosphorylation of Spaghetti squash (Sqh), the Drosophila MRLC orthologue, in vivo. The lethality of drak/rok mutants can be rescued by restoring Sqh activity, indicating that Sqh is the critical common effector of these two kinases. These results provide the first evidence that DAPK family kinases regulate actin dynamics in vivo and identify Drak as a novel component of the signaling networks that shape epithelial tissues.
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Neubueser
authors.forename: David R
authors.initials: DR
authors.lastname: Hipfner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D064550:Death-Associated Protein Kinases; D029721:Drosophila Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D024462:Myosin Type II / Q000378:metabolism; D010766:Phosphorylation; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D029721:Drosophila Proteins; C495593:Sqh protein, Drosophila; D064550:Death-Associated Protein Kinases; C555714:Drak protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D024462:Myosin Type II