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PMID:17202132
| Citation |
Li, T, Chalifour, LE and Paudel, HK (2007) Phosphorylation of protein phosphatase 1 by cyclin-dependent protein kinase 5 during nerve growth factor-induced PC12 cell differentiation. J. Biol. Chem. 282:6619-28 |
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| Abstract |
The transcription factor Egr-1 activates cyclin-dependent protein kinase 5 (Cdk5) during nerve growth factor (NGF)-induced differentiation of PC12 cells into neurons (Harada, T. Morooka, T., Ogawa, S., and Nishida, E. (2001) Nat. Cell Biol. 3, 453-459). The downstream target of Cdk5 in the Egr-1/Cdk5 pathway is not clear. In this study, we observed that phosphorylation of protein phosphatase 1 (PP1) on Thr(320) is reduced in brain extracts from Egr-1(-/-) mice, indicating that a kinase downstream of Egr-1 phosphorylates PP1. In HEK 293 cells co-transfected with PP1 and Cdk5, Cdk5 phosphorylates PP1. In vitro, Cdk5 purified from bovine brain phosphorylates bacterially expressed recombinant PP1. In NGF-treated PC12 cells, inhibition of Cdk5 by olomoucine or silencing Cdk5 expression by small interfering RNA strategy, suppresses PP1 phosphorylation. Silencing Cdk5 expression by small interfering RNA also blocks NGF-induced neurite outgrowth. Overexpression of PP1 (wild type) promotes NGF-induced differentiation of PC12 cells, whereas that of PP1 (T320A) has no effect. Our data indicate that PP1 is a downstream target of the NGF/Egr-1/Cdk5 pathway during NGF-induced differentiation of PC12 cells and suggest that PP1 phosphorylation promotes neuronal differentiation. |
| Links |
PubMed Online version:10.1074/jbc.M606347200 |
| Keywords |
Animals; Cattle; Cell Differentiation/drug effects; Cyclin-Dependent Kinase 5/metabolism; Early Growth Response Protein 1/metabolism; Humans; Mice; Mice, Knockout; Nerve Growth Factor/pharmacology; Neurons/cytology; PC12 Cells; Phosphoprotein Phosphatases/metabolism; Phosphorylation; Protein Phosphatase 1; Rats |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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