title: Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity.
abstract: Signal-induced activation of the transcription factor NF-kappaB requires specific phosphorylation of the inhibitor IkappaBalpha and its subsequent proteolytic degradation. Phosphorylation of serine residues 32 and 36 targets IkappaBalpha to the ubiquitin (Ub)-proteasome pathway. Here we report the identification of a large, multisubunit kinase (molecular mass approximately 700 kDa) that phosphorylates IkappaBalpha at S32 and S36. Remarkably, the activity of this kinase requires the Ub-activating enzyme (E1), a specific Ub carrier protein (E2) of the Ubc4/Ubc5 family, and Ub. We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IkappaBalpha. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis.
authors.affiliation: ProScript Incorporated, Cambridge, Massachusetts, 02139, USA.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Parent
authors.forename: T
authors.initials: T
authors.lastname: Maniatis
mesh_terms: D001665:Binding Sites / Q000502:physiology; D003593:Cytoplasm / Q000201:enzymology; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D008025:Ligases / Q000378:metabolism; D008970:Molecular Weight; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics
chemical_list: D016328:NF-kappa B; D014452:Ubiquitins; D012694:Serine; D044763:Ubiquitin-Conjugating Enzymes; C063109:ubiquitin-conjugating enzyme UBC4; D011494:Protein Kinases; D008025:Ligases