Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains.
The atypical cadherin Fat acts as a receptor for a signaling pathway that regulates growth, gene expression, and planar cell polarity. Genetic studies in Drosophila identified the four-jointed gene as a regulator of Fat signaling. We show that four-jointed encodes a protein kinase that phosphorylates serine or threonine residues within extracellular cadherin domains of Fat and its transmembrane ligand, Dachsous. Four-jointed functions in the Golgi and is the first molecularly defined kinase that phosphorylates protein domains destined to be extracellular. An acidic sequence motif (Asp-Asn-Glu) within Four-jointed was essential for its kinase activity in vitro and for its biological activity in vivo. Our results indicate that Four-jointed regulates Fat signaling by phosphorylating cadherin domains of Fat and Dachsous as they transit through the Golgi.
Ishikawa
Hiroyuki O
HO
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
Takeuchi
Hideyuki
H
Haltiwanger
Robert S
RS
Irvine
Kenneth D
KD
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D024202:Electrophoretic Mobility Shift Assay; D006031:Glycosylation; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism
D015820:Cadherins; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; C094449:ds protein, Drosophila; C095900:fj protein, Drosophila; C472307:ft protein, Drosophila; D013912:Threonine; D012694:Serine; D011494:Protein Kinases