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• W2148910325 abstract "Cyclin-dependent kinase 5 (Cdk5) plays a key role in the development of the mammalian nervous system; it phosphorylates a number of targeted proteins involved in neuronal migration during development to synaptic activity in the mature nervous system. Its role in the initial stages of neuronal commitment and differentiation of neural stem cells (NSCs), however, is poorly understood. In this study, we show that Cdk5 phosphorylation of p27 Kip1 at Thr187 is crucial to neural differentiation because 1) neurogenesis is specifically suppressed by transfection of p27 Kip1 siRNA into Cdk5 +/+ NSCs; 2) reduced neuronal differentiation in Cdk5 −/− compared with Cdk5 +/+ NSCs; 3) Cdk5 +/+ NSCs, whose differentiation is inhibited by a nonphosphorylatable mutant, p27/Thr187A, are rescued by cotransfection of a phosphorylation-mimicking mutant, p27/Thr187D; and 4) transfection of mutant p27 Kip1 (p27/187A) into Cdk5 +/+ NSCs inhibits differentiation. These data suggest that Cdk5 regulates the neural differentiation of NSCs by phosphorylation of p27 Kip1 at theThr187 site. Additional experiments exploring the role of Ser10 phosphorylation by Cdk5 suggest that together with Thr187 phosphorylation, Ser10 phosphorylation by Cdk5 promotes neurite outgrowth as neurons differentiate. Cdk5 phosphorylation of p27 Kip1 , a modular molecule, may regulate the progress of neuronal differentiation from cell cycle arrest through differentiation, neurite outgrowth, and migration." @default.
• W2148910325 created "2016-06-24" @default.
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• W2148910325 date "2010-10-15" @default.
• W2148910325 modified "2023-10-03" @default.
• W2148910325 title "Phosphorylation of p27^Kip1at Thr187 by Cyclin-dependent Kinase 5 Modulates Neural Stem Cell Differentiation" @default.
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• W2148910325 doi "https://doi.org/10.1091/mbc.e10-01-0054" @default.
• W2148910325 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2954124" @default.
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