title: Phosphorylation and activation of the atypical kinase p53-related protein kinase (PRPK) by Akt/PKB.
abstract: p53-related protein kinase (PRPK), the human homologue of yeast Bud32, belonging to a small subfamily of atypical protein kinases, is inactive unless it is previously incubated with cell lysates. Here we show that such an activation of PRPK is mediated by another kinase, Akt/PKB, which phosphorylates PRPK at Ser250. We show that recombinant PRPK is phosphorylated in vitro by Akt and its phospho-form is recognized by a Ser250-phospho-specific antibody; that cell co-transfection with Akt along with wild-type PRPK, but not with its Ser250Ala mutant, results in increased PRPK phosphorylation; and that the phosphorylation of p53 at Ser15, the only known substrate of PRPK, is markedly increased by co-transfection of Akt with wild-type PRPK, but not PRPK dead mutant, and is abrogated by cell treatment with the Akt pathway inhibitor LY294002. Our data disclose an unanticipated mechanism by which PRPK can be activated and provide a functional link between this enigmatic kinase and the Akt signaling pathway.
authors: Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, Viale G. Colombo 3, 35121, Padova, Italy.
authors: S
authors: S
authors: Facchin
authors: M
authors: M
authors: Ruzzene
authors: C
authors: C
authors: Peggion
authors: G
authors: G
authors: Sartori
authors: G
authors: G
authors: Carignani
authors: O
authors: O
authors: Marin
authors: F
authors: F
authors: Brustolon
authors: R
authors: R
authors: Lopreiato
authors: L A
authors: LA
authors: Pinna
mesh_terms: D002384:Catalysis; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014161:Transduction, Genetic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012694:Serine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C441644:TP53RK protein, human