The novel ankyrin-repeat containing kinase ARCK-1 acts as a suppressor of the Spalten signaling pathway during Dictyostelium development.
Spalten (Spn), a member of the PP2C family of Ser/Thr protein phosphatases, is required for Dictyostelium cell-type differentiation and morphogenesis. We have identified a new protein kinase, ARCK-1, through a second site suppressor screen for mutants that allow spn null cells to proceed further through development. ARCK-1 has a C-terminal kinase domain most closely related to Ser/Thr protein kinases and an N-terminal putative regulatory domain with ankyrin repeats, a 14-3-3 binding domain, and a C1 domain, which is required for binding to RasBGTP in a two-hybrid assay. Disruption of the gene encoding ARCK-1 results in weak, late developmental defects. However, overexpression of ARCK-1 phenocopies the spn null phenotype, consistent with Spn and ARCK-1 being on the same developmental pathway. Our previous analyses of Spn and the present analysis of ARCK-1 suggest a model in which Spn and ARCK-1 differentially control the phosphorylation state of a protein that regulates cell-type differentiation. Dephosphorylation of the substrate by Spn is required for cell-type differentiation. Control of ARCK-1 and Spn activities by upstream signals is proposed to be part of the developmental regulatory program mediating cell-fate decisions in Dictyostelium.
Laboratoire de Biochimie et Biophysique des Systèmes Intégrés (UMR 5092 CNRS-CEA-UJF), DRDC/BBSI, CEA-Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France.
Laurence
L
Aubry
Susan
S
Lee
Kissia
K
Ravanel
Richard A
RA
Firtel
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D017089:Ankyrin Repeat; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004023:Dictyostelium / Q000201:enzymology* / Q000502:physiology; D005656:Fungal Proteins; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D048948:14-3-3 Proteins; D005656:Fungal Proteins; D015800:Protozoan Proteins; C112495:SPNA protein, Dictyostelium discoideum; C489016:ras protein, Dictyostelium; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D018631:ras Proteins