PMID- 17202132
OWN - NLM
STAT- MEDLINE
DCOM- 20070618
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 9
DP  - 2007 Mar 2
TI  - Phosphorylation of protein phosphatase 1 by cyclin-dependent protein kinase 5 
      during nerve growth factor-induced PC12 cell differentiation.
PG  - 6619-28
AB  - 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.
FAU - Li, Tong
AU  - Li T
AD  - Bloomfield Center for Research in Aging, Lady Davis Institute for Medical 
      Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Canada.
FAU - Chalifour, Lorraine E
AU  - Chalifour LE
FAU - Paudel, Hemant K
AU  - Paudel HK
LA  - eng
PT  - Journal Article
DEP - 20070103
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Differentiation/*drug effects
MH  - Cyclin-Dependent Kinase 5/*metabolism
MH  - Early Growth Response Protein 1/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Growth Factor/*pharmacology
MH  - Neurons/cytology
MH  - PC12 Cells
MH  - Phosphoprotein Phosphatases/*metabolism
MH  - Phosphorylation
MH  - Protein Phosphatase 1
MH  - Rats
EDAT- 2007/01/05 09:00
MHDA- 2007/06/19 09:00
CRDT- 2007/01/05 09:00
PHST- 2007/01/05 09:00 [pubmed]
PHST- 2007/06/19 09:00 [medline]
PHST- 2007/01/05 09:00 [entrez]
AID - S0021-9258(20)52273-4 [pii]
AID - 10.1074/jbc.M606347200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Mar 2;282(9):6619-28. doi: 10.1074/jbc.M606347200. Epub 2007 
      Jan 3.