TY - JOUR
T1 - Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of cubitus interruptus
AU - Zhang, Wensheng
AU - Zhao, Yun
AU - Tong, Chao
AU - Wang, Gelin
AU - Wang, Bing
AU - Jia, Jianhang
AU - Jiang, Jin
N1 - Funding Information:
We thank Liping Luo for technical assistance; Drs. Dan Kalderon, L. Goldstein, P. Beachy, M. Scott, D. Virshup, M. Bourouis, J.R. Woodgett, J. Peters, P. Therond, and G. Struhl for reagents; and Dr. K. Wharton for comments on the manuscript. This work was supported by grants from the National Institutes of Health and the Leukemia and Lymphoma Society Scholar Program to Jin Jiang (J.J.). J.J. is also a Eugene McDermott Endowed Scholar in Biomedical Science at the University of Texas Southwestern.
PY - 2005/2
Y1 - 2005/2
N2 - Hedgehog (Hh) proteins control animal development by regulating the Gli/Ci family of transcription factors. In Drosophila, Hh counteracts phosphorylation by PKA, GSK3, and CKI to prevent Cubitus interruptus (Ci) processing through unknown mechanisms. Here, we show that these kinases physically interact with the kinesin-like protein Costal2 (Cos2) to control Ci processing and that Hh inhibits such interaction. Cos2 is required for Ci phosphorylation in vivo, and Cos2-immunocomplexes (Cos2IPs) phosphorylate Ci and contain PKA, GSK3, and CKI. By using a Kinesin-Cos2 chimeric protein that carries Cos2-interacting proteins to the microtubule plus end, we demonstrated that these kinases bind Cos2 in intact cells. PKA, GSK3, and CKI directly bind the N- and C-terminal regions of Cos2, both of which are essential for Ci processing. Finally, we showed that Hh signaling inhibits Cos2-kinase complex formation. We propose that Cos2 recruits multiple kinases to efficiently phosphorylate Ci and that Hh inhibits Ci phosphorylation by specifically interfering with kinase recruitment.
AB - Hedgehog (Hh) proteins control animal development by regulating the Gli/Ci family of transcription factors. In Drosophila, Hh counteracts phosphorylation by PKA, GSK3, and CKI to prevent Cubitus interruptus (Ci) processing through unknown mechanisms. Here, we show that these kinases physically interact with the kinesin-like protein Costal2 (Cos2) to control Ci processing and that Hh inhibits such interaction. Cos2 is required for Ci phosphorylation in vivo, and Cos2-immunocomplexes (Cos2IPs) phosphorylate Ci and contain PKA, GSK3, and CKI. By using a Kinesin-Cos2 chimeric protein that carries Cos2-interacting proteins to the microtubule plus end, we demonstrated that these kinases bind Cos2 in intact cells. PKA, GSK3, and CKI directly bind the N- and C-terminal regions of Cos2, both of which are essential for Ci processing. Finally, we showed that Hh signaling inhibits Cos2-kinase complex formation. We propose that Cos2 recruits multiple kinases to efficiently phosphorylate Ci and that Hh inhibits Ci phosphorylation by specifically interfering with kinase recruitment.
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U2 - 10.1016/j.devcel.2005.01.001
DO - 10.1016/j.devcel.2005.01.001
M3 - Article
C2 - 15691767
AN - SCOPUS:13344261322
SN - 1534-5807
VL - 8
SP - 267
EP - 278
JO - Developmental cell
JF - Developmental cell
IS - 2
ER -