title: Regulation of Drosophila Development by the Golgi Kinase Four-Jointed.
abstract: Despite intensive research on kinases and protein phosphorylation, most studies focus on kinases localized to the cytosol and nucleus. Studies in Drosophila discovered a novel signaling pathway that regulates growth and planar cell polarity. In this pathway, the atypical cadherin Fat acts as a receptor, and the cadherin Dachsous (Ds) serves as its ligand. Genetic studies in Drosophila identified the four-jointed gene as a regulator of the Fat pathway. Four-jointed (Fj) resides in the Golgi and phosphorylates the cadherin domains of Fat and Ds. Fj-mediated phosphorylations promote the ability of Fat to bind to its ligand Ds and inhibit the ability of Ds to bind Fat, which is biased toward a stronger effect on Fat. Fj is expressed in a gradient in many developing tissues. The Fat-Ds-binding gradient can be explained by the graded activity of Fj that is sufficient to propagate the polarization of complexes across whole tissues. Recent studies revealed a new class of kinases that localize within the secretory pathway and the extracellular space, and phosphorylate proteins and sugar chains in the secretory pathway. Further, they appear to regulate extracellular processes. Mutations of the genes encoding these kinases cause human disease, thus underscoring the biological importance of phosphorylation events within the secretory pathway.
authors.affiliation: Graduate School of Science, Chiba University, Chiba, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Keira
authors.affiliation: Graduate School of Science, Chiba University, Chiba, Japan.
authors.forename: Moe
authors.initials: M
authors.lastname: Wada
authors.affiliation: Graduate School of Science, Chiba University, Chiba, Japan. Electronic address: ishikawaho@faculty.chiba-u.jp.
authors.forename: Hiroyuki O
authors.initials: HO
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D047108:Embryonic Development; D006056:Golgi Apparatus / Q000201:enzymology*; D006801:Humans; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014714:Vertebrates / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D011494:Protein Kinases
keywords: Cadherin; Dachsous; Fat; Four-jointed; Golgi kinase; Growth control; Planar cell polarity; Secretory pathway