Ci Proteolysis: Regulation by a Constellation of Phosphorylation Sites
نویسندگان
چکیده
Proteolytic processing of Ci requires phosphorylation by the kinases Sgg/GSK3 and CK1. The newly identified phosphorylation sites form clusters with previously described PKA sites in which phosphorylation by PKA acts to prime subsequent phosphorylation by Sgg/GSK3 and CK1.
منابع مشابه
Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedgehog pathway activity by Ci phosphorylation.
Hedgehog (Hh) proteins signal by inhibiting the proteolytic processing of Ci/Gli family transcription factors and by increasing Ci/Gli-specific activity. When Hh is absent, phosphorylation of Ci/Gli triggers binding to SCF ubiquitin ligase complexes and consequent proteolysis. Here we show that multiple successively phosphorylated CK1 sites on Ci create an atypical extended binding site for the...
متن کاملProteolysis of the Hedgehog Signaling Effector Cubitus interruptus Requires Phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1
The secreted signaling molecule Hedgehog regulates gene expression in target cells in part by preventing proteolysis of the full-length Cubitus interruptus (Ci-155) transcriptional activator to the Ci-75 repressor form. Ci-155 proteolysis depends on phosphorylation at three sites by Protein Kinase A (PKA). We show that these phosphoserines prime further phosphorylation at adjacent Glycogen Synt...
متن کاملProtein kinase A directly regulates the activity and proteolysis of cubitus interruptus.
Cubitus interruptus (Ci) is a transcriptional factor that is positively regulated by the hedgehog (hh) signaling pathway. Recent work has shown that a 75-kDa proteolytic product of the full-length CI protein translocates to the nucleus and represses the transcription of CI target genes. In cells that receive the hh signal, the proteolysis of CI is inhibited and the full-length protein can activ...
متن کاملProcessing of the Drosophila Hedgehog Signaling Effector Ci-155 to the Repressor Ci-75 Is Mediated by Direct Binding to the SCF Component Slimb
Signaling by extracellular Hedgehog (Hh) molecules is crucial for the correct allocation of cell fates and patterns of cell proliferation in humans and other organisms . Responses to Hh are universally mediated by regulating the activity and the proteolysis of the Gli family of transcriptional activators such that they induce target genes only in the presence of Hh . In the absence of Hh, the s...
متن کاملGenetic evidence for a protein kinase A/cubitus interruptus complex that facilitates processing of cubitus interruptus in Drosophila.
Hedgehog (Hh) activates a signal transduction pathway regulating Cubitus interruptus (Ci). In the absence of Hh, full-length Ci (Ci-155) is bound in a complex that includes Costal2 (Cos2) and Fused (Fu). Ci-155 is phosphorylated by protein kinase A (PKA), inducing proteolysis to Ci-75, a transcriptional repressor. Hh signaling blocks proteolysis and produces an activated Ci-155 transcriptional ...
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ورودعنوان ژورنال:
- Current Biology
دوره 12 شماره
صفحات -
تاریخ انتشار 2002