PMID- 17209049
OWN - NLM
STAT- MEDLINE
DCOM- 20070413
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 10
DP  - 2007 Mar 9
TI  - AKT and CDK5/p35 mediate brain-derived neurotrophic factor induction of DARPP-32 
      in medium size spiny neurons in vitro.
PG  - 7352-9
AB  - Mature striatal medium size spiny neurons express the dopamine and cyclic 
      AMP-regulated phosphoprotein, 32 kDa (DARPP-32), but little is known about the 
      mechanisms regulating its levels or the specification of fully differentiated 
      neuronal subtypes. Cell extrinsic molecules that increase DARPP-32 mRNA and/or 
      protein levels include brain-derived neurotrophic factor (BDNF), retinoic acid, 
      and estrogen. DARPP-32 induction by BDNF in vitro requires phosphatidylinositide 
      3-kinase (PI3K), but inhibition of phosphorylation of protein kinase B/Akt does 
      not entirely abolish expression of DARPP-32. Moreover, the requirement for Akt 
      has not been established. Using pharmacologic inhibitors of PI3K, Akt, and 
      cyclin-dependent kinase 5 (cdk5) and constitutively active and dominant negative 
      PI3K, Akt, cdk5, and p35 viruses in cultured striatal neurons, we measured 
      BDNF-induced levels of DARPP-32 protein and/or mRNA. We demonstrated that both 
      the PI3K/Akt/mammalian target of rapamycin and the cdk5/p35 signal transduction 
      pathways contribute to the induction of DARPP-32 protein levels by BDNF and that 
      the effects are on both the transcriptional and translational levels. It also 
      appears that PI3K is upstream of cdk5/p35, and its activation can lead to an 
      increase in p35 protein levels. These data support the presence of multiple 
      signal transduction pathways mediating expression of DARPP-32 in vitro, including 
      a novel, important pathway via by which PI3K regulates the contribution of 
      cdk5/p35.
FAU - Bogush, Alexey
AU  - Bogush A
AD  - Farber Institute for Neurosciences and Department of Neurology, Thomas Jefferson 
      University, Philadelphia, Pennsylvania 19107, USA.
FAU - Pedrini, Steve
AU  - Pedrini S
FAU - Pelta-Heller, Joshua
AU  - Pelta-Heller J
FAU - Chan, Tung
AU  - Chan T
FAU - Yang, Qian
AU  - Yang Q
FAU - Mao, Zixu
AU  - Mao Z
FAU - Sluzas, Emily
AU  - Sluzas E
FAU - Gieringer, Tracy
AU  - Gieringer T
FAU - Ehrlich, Michelle E
AU  - Ehrlich ME
LA  - eng
GR  - AG023695/AG/NIA NIH HHS/United States
GR  - R01NS045942/NS/NINDS NIH HHS/United States
GR  - R01NS048254/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070105
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Androstadienes)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Ppp1r1b protein, mouse)
RN  - 0 (neuronal Cdk5 activator (p25-p35))
RN  - 03L9OT429T (Rotenone)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (Cdk5 protein, mouse)
RN  - K5Z93K66IE (deguelin)
RN  - W36ZG6FT64 (Sirolimus)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase 5/*physiology
MH  - Dopamine and cAMP-Regulated Phosphoprotein 32/*biosynthesis
MH  - Huntington Disease/drug therapy
MH  - Mice
MH  - Nerve Tissue Proteins/*physiology
MH  - Neurons/*metabolism
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Protein Kinases/physiology
MH  - Proto-Oncogene Proteins c-akt/*physiology
MH  - Rotenone/analogs & derivatives/pharmacology
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Wortmannin
EDAT- 2007/01/09 09:00
MHDA- 2007/04/17 09:00
CRDT- 2007/01/09 09:00
PHST- 2007/01/09 09:00 [pubmed]
PHST- 2007/04/17 09:00 [medline]
PHST- 2007/01/09 09:00 [entrez]
AID - S0021-9258(20)63576-1 [pii]
AID - 10.1074/jbc.M606508200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Mar 9;282(10):7352-9. doi: 10.1074/jbc.M606508200. Epub 2007 
      Jan 5.