PMID- 10585422
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 50
DP  - 1999 Dec 10
TI  - Adenosine A(2A) receptor mRNA regulation by nerve growth factor is TrkA-, Src-,
      and Ras-dependent via extracellular regulated kinase and stress-activated protein
      kinase/c-Jun NH(2)-terminal kinase.
PG  - 35499-504
AB  - We have shown previously that nerve growth factor (NGF) down-regulates adenosine 
      A(2A) receptor (A(2A)AR) mRNA in PC12 cells. To define cellular mechanisms that
      modulate A(2A)AR expression, A(2A)AR mRNA and protein levels were examined in
      three PC12 sublines: i) PC12nnr5 cells, which lack the high affinity NGF receptor
      TrkA, ii) srcDN2 cells, which overexpress kinase-defective Src, and iii) 17.26
      cells, which overexpress a dominant-inhibitory Ras. In the absence of functional 
      TrkA, Src, or Ras, NGF-induced down-regulation of A(2A)AR mRNA and protein was
      significantly impaired. However, regulation of A(2A)AR expression was
      reconstituted in PC12nnr5 cells stably transfected with TrkA. Whereas NGF
      stimulated the mitogen-activated protein kinases p38, extracellular regulated
      kinase 1 and 2 (ERK1/ERK2), and stress-activated protein kinase/c-Jun
      NH(2)-terminal kinase (SAPK/JNK) in PC12 cells, these kinases were activated only
      partially or not at all in srcDN2 and 17.26 cells. Inhibiting ERK1/ERK2 with
      PD98059 or inhibiting SAPK/JNK by transfecting cells with a dominant-negative
      SAPKbeta/JNK3 mutant partially blocked NGF-induced down-regulation of A(2A)AR
      expression in PC12 cells. In contrast, inhibiting p38 with SB203580 had no effect
      on the regulation of A(2A)AR mRNA and protein levels. Treating SAPKbeta/JNK3
      mutant-transfected PC12 cells with PD98059 completely abolished the NGF-induced
      decrease in A(2A)AR mRNA and protein levels. These results reveal a role for
      ERK1/ERK2 and SAPK/JNK in regulating A(2A)AR expression.
FAU - Malek, R L
AU  - Malek RL
AD  - Department of Molecular and Cellular Biology, The Institute for Genomic Research,
      Rockville, Maryland 20850, USA.
FAU - Nie, Z
AU  - Nie Z
FAU - Ramkumar, V
AU  - Ramkumar V
FAU - Lee, N H
AU  - Lee NH
LA  - eng
GR  - HL56316/HL/NHLBI NIH HHS/United States
GR  - NS352321/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Receptors, Purinergic P1)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Down-Regulation
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Nerve Growth Factors/*pharmacology
MH  - PC12 Cells
MH  - Rats
MH  - Receptor, Adenosine A2A
MH  - Receptor, trkA/*physiology
MH  - Receptors, Purinergic P1/*genetics
MH  - Recombinant Proteins/metabolism
MH  - Transcription, Genetic/*drug effects
MH  - Transfection
MH  - ras Proteins/*metabolism
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1074/jbc.274.50.35499 [doi]
AID - S0021-9258(19)53273-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 10;274(50):35499-504. doi: 10.1074/jbc.274.50.35499.