Casein kinase 2 promotes Hedgehog signaling by regulating both smoothened and Cubitus interruptus.
Casein kinase 2 (CK2) is a typical serine/threonine kinase consisting of α and β subunits and has been implicated in many cellular and developmental processes. In this study, we demonstrate that CK2 is a positive regulator of the Hedgehog (Hh) signal transduction pathway. We found that inactivation of CK2 by CK2β RNAi enhances the loss-of-Hh wing phenotype induced by a dominant negative form of Smoothened (Smo). CK2β RNAi attenuates Hh-induced Smo accumulation and down-regulates Hh target gene expression, whereas increasing CK2 activity by coexpressing CK2α and CK2β increases Smo accumulation and induces ectopic Hh target gene expression. We identified the serine residues in Smo that can be phosphorylated by CK2 in vitro. Mutating these serine residues attenuates the ability of Smo to transduce high level Hh signaling activity in vivo. Furthermore, we found that CK2 plays an additional positive role downstream of Smo by regulating the stability of full-length Cubitus interruptus (Ci). CK2β RNAi promotes Ci degradation whereas coexpressing CK2α and CK2β increases the half-life of Ci. We showed that CK2 prevents Ci ubiquitination and degradation by the proteasome. Thus, CK2 promotes Hh signaling activity by regulating multiple pathway components.
Jia
Hongge
H
Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536, USA.
Liu
Yajuan
Y
Xia
Ruohan
R
Tong
Chao
C
Yue
Tao
T
Jiang
Jin
J
Jia
Jianhang
J
D000818:Animals; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D014157:Transcription Factors; C092937:ci protein, Drosophila; C100664:smo protein, Drosophila; D047390:Casein Kinase II