PMID- 15389548
OWN - NLM
STAT- MEDLINE
DCOM- 20041214
LR  - 20091119
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 201
IP  - 3
DP  - 2004 Dec
TI  - Multiple signaling conduits regulate global differentiation-specific gene 
      expression in PC12 cells.
PG  - 459-69
AB  - PC12 cells serve as a model for exploring nerve growth factor (NGF)-stimulated 
      signal pathways that mediate neural differentiation. We previously demonstrated 
      that neurofilament light chain (NFLC) gene induction by NGF requires 
      collaborative extracellular signal-regulated kinase (ERK) and c-Jun N-terminal 
      kinase (JNK) signaling. Herein, we investigate the broader requirement for 
      integrated ERK and JNK signaling in NGF-stimulated gene expression. NGF 
      stimulates differentiation as well as maintenance of cell viability while 
      insulin-like growth factor-1 (IGF-1) stimulates only trophic actions in PC12 
      cells. Affymetrix Genechips were used to identify genes whose expression 
      specifically increased in response to NGF, but not IGF-1. From the set of 
      NGF-specific genes, the induction by NGF of ten genes with diverse predicted 
      cellular functions was tested for ERK and JNK pathway requirements using the 
      protein kinase inhibitors, PD98059 and SP600125, respectively. Like NFLC, 
      induction of urokinase plasminogen activator (uPAR), transin/matrix 
      metalloproteinase 3 (MMP3), Fra-1 and transforming growth factor beta 1 (TGF beta 
      1) required collaborative ERK and JNK signaling while the increased expression of 
      cortexin, rat collapsin response mediator protein 4 (rCRMP4), rat growth and 
      transformation-dependent protein (RGT), and synapsin II required neither 
      mitogen-activated protein kinase (MAPK) pathway. NGF-induction of the bradykinin 
      B2 receptor and c-Ret mRNAs was partially inhibited by SP600125, but not PD98059. 
      Reporter constructs containing the promoters for ERK/JNK-dependent genes (NFLC, 
      transin, uPAR) as well as an ERK/JNK-independent gene (synapsin II) revealed that 
      both sets of genes required functional Ras signaling for activation by NGF. 
      Integrated signaling through the ERK and JNK MAPKs, therefore, represents a 
      general conduit for NGF-dependent gene expression, but additional Ras-dependent 
      signaling pathways distinct from the ERKs and JNKs must contribute as well. Thus, 
      multiple signaling conduits control global differentiation-specific gene 
      expression in PC12 cells.
FAU - Marek, Lindsay
AU  - Marek L
AD  - Department of Medicine, University of Colorado Health Sciences Center, Denver, 
      Colorado 80262, USA.
FAU - Levresse, Valerie
AU  - Levresse V
FAU - Amura, Claudia
AU  - Amura C
FAU - Zentrich, Eve
AU  - Zentrich E
FAU - Van Putten, Vicki
AU  - Van Putten V
FAU - Nemenoff, Raphael A
AU  - Nemenoff RA
FAU - Heasley, Lynn E
AU  - Heasley LE
LA  - eng
GR  - DK59756/DK/NIDDK NIH HHS/United States
GR  - GM61718/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Synapsins)
RN  - 0 (fos-related antigen 1)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Nerve Growth Factor/*pharmacology
MH  - *Oligonucleotide Array Sequence Analysis
MH  - PC12 Cells
MH  - Polymerase Chain Reaction
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Rats
MH  - Signal Transduction/*drug effects
MH  - Synapsins/metabolism
MH  - Transcriptional Activation
EDAT- 2004/09/25 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/09/25 05:00
PHST- 2004/09/25 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/09/25 05:00 [entrez]
AID - 10.1002/jcp.20087 [doi]
PST - ppublish
SO  - J Cell Physiol. 2004 Dec;201(3):459-69. doi: 10.1002/jcp.20087.