scholarly journals Nerve growth factor regulates the expression and activity of p33cdk2 and p34cdc2 kinases in PC12 pheochromocytoma cells.

1994 ◽  
Vol 5 (11) ◽  
pp. 1225-1241 ◽  
Author(s):  
K J Buchkovich ◽  
E B Ziff
Keyword(s):  
Transcription Factor ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
Negative Regulator ◽  
Regulatory Subunit ◽  
Nerve Growth ◽  
Cyclin Dependent Kinases ◽  
Cell Cycling ◽  
Pc12 Differentiation

In the absence of serum, nerve growth factor (NGF) promotes the survival and differentiation of the PC12 pheochromocytoma cell line. In the presence of serum, NGF acts primarily as a differentiation factor and negative regulator of cell cycling. To investigate NGF control of cell cycling, we have analyzed the regulation of cyclin dependent kinases during PC12 cell differentiation. NGF treatment leads to a reduction in the steady-state protein levels of p33cdk2 and p34cdc2, two key regulators of cell cycle progression. The decrease in p33cdk2 and p34cdc2 coincides with a decrease in the enzymatic activity of cyclinA-p34cdc2, cyclinB-p34cdc2, cyclinE-p33cdk2, and cyclinA-p33cdk2 kinases. The decline in p33cdk2 and p34cdc2 kinase activity in response to NGF is accelerated in cells that over-express the p140trk NGF receptor, suggesting that the timing of the down- regulation is dependent on the level of p140trk and the strength of the NGF signal. The level of cyclin A, a regulatory subunit of p33cdk2 and p34cdc2, is relatively constant during PC12 differentiation. Nevertheless, the DNA binding activity of the cyclinA-associated transcription factor E2F/DP decreases. Thus, NGF down-regulates the activity of cyclin dependent kinases and cyclin-transcription factor complexes during PC12 differentiation.

scholarly journals Nerve Growth Factor Activates Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Pathways To Stimulate CREB Serine 133 Phosphorylation

1998 ◽  
Vol 18 (4) ◽  
pp. 1946-1955 ◽  
Author(s):  
Jun Xing ◽  
Jon M. Kornhauser ◽  
Zhengui Xia ◽  
Elizabeth A. Thiele ◽  
Michael E. Greenberg
Keyword(s):  
Transcription Factor ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Nerve Growth ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Ribosomal S6 Kinase

ABSTRACT The mechanisms by which growth factor-induced signals are propagated to the nucleus, leading to the activation of the transcription factor CREB, have been characterized. Nerve growth factor (NGF) was found to activate multiple signaling pathways that mediate the phosphorylation of CREB at the critical regulatory site, serine 133 (Ser-133). NGF activates the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPKs), which in turn activate the pp90 ribosomal S6 kinase (RSK) family of Ser/Thr kinases, all three members of which were found to catalyze CREB Ser-133 phosphorylation in vitro and in vivo. In addition to the ERK/RSK pathway, we found that NGF activated the p38 MAPK and its downstream effector, MAPK-activated protein kinase 2 (MAPKAP kinase 2), resulting in phosphorylation of CREB at Ser-133. Inhibition of either the ERK/RSK or the p38/MAPKAP kinase 2 pathway only partially blocked NGF-induced CREB Ser-133 phosphorylation, suggesting that either pathway alone is sufficient for coupling the NGF signal to CREB activation. However, inhibition of both the ERK/RSK and the p38/MAPKAP kinase 2 pathways completely abolished NGF-induced CREB Ser-133 phosphorylation. These findings indicate that NGF activates two distinct MAPK pathways, both of which contribute to the phosphorylation of the transcription factor CREB and the activation of immediate-early genes.

scholarly journals Regulation of Id1 and its association with basic helix-loop-helix proteins during nerve growth factor-induced differentiation of PC12 cells.

1995 ◽  
Vol 15 (8) ◽  
pp. 4175-4183 ◽  
Author(s):  
M B Einarson ◽  
M V Chao
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cell ◽  
Negative Regulator ◽  
Cdna Expression Library ◽  
Mobility Shift ◽  
Expression Library ◽  
Nerve Growth ◽  
Helix Loop Helix ◽  
Nuclear Extracts

Cell differentiation in the nervous system is dictated by specific patterns of gene expression. We have investigated the role of helix-loop-helix (HLH) proteins during differentiation of PC12 pheochromocytoma cells in response to nerve growth factor. Gel mobility shift assays using PC12 cell nuclear extracts demonstrated that active basic HLH complexes exist throughout differentiation. Addition of exogeneous Id1 protein, a negative regulator of basic HLH proteins, disrupted specific complexes formed by PC12 cell nuclear extracts on a CANNTG consensus oligonucleotide. To identify possible novel basic HLH proteins in these complexes, a glutathione S-transferase-Id1 fusion protein was used to screen a PC12 cell cDNA expression library. A single clone representing the rat E2-2 gene was identified. Sequential immunoprecipitations with antibodies to each HLH protein revealed an association between Id1 and E2-2 that could be detected in both untreated and nerve growth factor-treated PC12 cell lysates. These experiments define a new HLH interaction between Id1 and E2-2 in neuronal cells and suggest that neuronal differentiation may be regulated by HLH proteins in a distinctive manner.

scholarly journals Activation of codependent transcription factors is required for transcriptional induction of the vgf gene by nerve growth factor and Ras.

1996 ◽  
Vol 16 (9) ◽  
pp. 4621-4631 ◽  
Author(s):  
G D'Arcangelo ◽  
R Habas ◽  
S Wang ◽  
S Halegoua ◽  
S R Salton
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Mutational Analysis ◽  
Globin Gene ◽  
Beta Globin ◽  
Nerve Growth ◽  
Transcriptional Induction

Nerve growth factor (NGF) treatment of PC12 cells leads to the elaboration of a neuronal phenotype, including the induction of neuronally expressed genes such as vgf. To study vgf transcription, we have created chimeric vgf/beta-globin genes in which vgf promoter sequences drive the expression of the beta-globin reporter gene or of a chimeric beta-globin gene fused to 3' untranslated vgf gene sequences. We have found that the level of inducibility of the latter construct by NGF resembles that of the endogenous vgf gene. Using transient transfection of the chimeric reporter genes into PC12 cells, into PC12 subclones expressing activated or dominantly interfering mutant Ras proteins, and into PC12 variants expressing specific NGF receptor/Trk mutants, we show that transcriptional regulation of the vgf promoter by NGF is mediated through a Ras-dependent signaling pathway. By mutational analysis of the vgf promoter, we have identified three promoter elements involved in mediating transcriptional induction by NGF and Ras. In addition to the cyclic AMP-responsive element (CRE), which binds to ATF-1, ATF-2, and CRE-binding protein in PC12 nuclear extracts, a novel CCAAT element and its binding proteins were identified, which, like the CRE, is necessary but not sufficient for the Ras-dependent induction of the vgf gene by NGF. We also identify a G(S)G element unusually located between the TATA box and transcriptional start site, which binds the NGF- and Ras-induced transcription factor, NGFI-A, and amplifies the transcriptional response. Integrating data from studies of vgf promoter regulation and NGF signal transduction, we present a model for vgf gene induction in which transcriptional activation is achieved through the persistent, direct activation of multiple interacting transcription factors binding to CRE and CCAAT elements, coordinated with the delayed transcription factor action at a G(S)G element resulting from the induced expression of NGFI-A.

Regulation of the transcription factor c-JUN by nerve growth factor in adult sensory neurons

1993 ◽  
Vol 154 (1-2) ◽  
pp. 129-133 ◽  
Author(s):  
Bruce G. Gold ◽  
Toni Storm-Dickerson ◽  
Daniel R. Austin
Keyword(s):  
Transcription Factor ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sensory Neurons ◽  
Nerve Growth ◽  
Factor C

Molecular Cloning, Expression, and Characterization of Rat Homolog of Human AP-2α That Stimulates Neuropeptide Y Transcription Activity in Response to Nerve Growth Factor

2000 ◽  
Vol 14 (6) ◽  
pp. 837-847
Author(s):  
Bing-Sheng Li ◽  
Phillip R. Kramer ◽  
Weiqin Zhao ◽  
Wu Ma ◽  
David A. Stenger ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neuropeptide Y ◽  
Nuclear Protein ◽  
Nerve Growth ◽  
Transcription Activity ◽  
Promoter Gene ◽  
Human Transcription Factor

Abstract Neuropeptide Y (NPY) plays an important role in the central regulation of neuronal activity, endocrine and sexual behavior, and food intake. Although transcription activity of the NPY gene in PC12 cells is regulated by a number of agents such as nerve growth factor (NGF), the mechanism responsible for the NGF-elicited increase in the transcription of the NPY gene remains to be explored. In this study, we isolated and characterized a nuclear protein that is bound to NGF-response elements (NGFRE) that lie between nucleotide −87 and −33 of the rat NPY promoter gene. This nuclear protein is identical to the rat homolog of human transcription factor AP-2α. We further demonstrated that rat AP-2α promotes efficient NPY transcription activity in response to NGF. Finally, we provide direct evidence that the mice lacking transcription factor AP-2α exhibit reduced expression of NPY mRNA compared with wild-type mice, further supporting the hypothesis that AP-2α is an important transcription factor in regulating NPY transcription activity.

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