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Science 18 July 2008:
Vol. 321. no. 5887, pp. 401 - 404
DOI: 10.1126/science.1158159
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Reports

Four-jointed Is a Golgi Kinase That Phosphorylates a Subset of Cadherin Domains

Hiroyuki O. Ishikawa,1 Hideyuki Takeuchi,2 Robert S. Haltiwanger,2 Kenneth D. Irvine1*

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.

1 Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
2 Department of Biochemistry and Cell Biology, Institute for Cell and Developmental Biology, Stony Brook University, Stony Brook, NY 11794, USA.

* To whom correspondence should be addressed. E-mail: irvine{at}waksman.rutgers.edu

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