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PMID: 2538715 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Nerve growth factor regulates gene expression by several distinct mechanisms.

Molecular and cellular biology ·Vol. 9 ·No. 1 ·1989-01-00 ·Pages 135-43

Cho KO, Skarnes WC, Minsk B, Palmieri S, Jackson-Grusby L, Wagner JA

Abstract

To help elucidate the mechanisms by which nerve growth factor (NGF) regulates gene expression, we have identified and studied four genes (a-2, d-2, d-4, and d-5) that are positively regulated by NGF in PC12 cells, including one (d-2) which has previously been identified as a putative transcription factor (NGF I-A). Three of these genes, including d-2, were induced very rapidly at the transcriptional level, but the relative time courses of transcription and mRNA accumulation of each of these three genes were distinct. The fourth gene (d-4) displayed no apparent increase in transcription that corresponded to the increase in its mRNA, suggesting that NGF may regulate its expression at a posttranscriptional level. Thus, NGF positively regulates gene expression by more than one mechanism. These genes could also be distinguished on the basis of their response to cyclic AMP. The expression of d-2 and a-2 was increased by cholera toxin and further augmented by NGF; however, cholera toxin not only failed to increase the levels of d-5 and d-4 mRNA but also actually inhibited the NGF-dependent increase. The expression of each of these genes, including d-2 (NGF I-A), was also increased by fibroblast growth factor, epidermal growth factor (EGF), phorbol myristate acetate, and in some cases insulin, showing that the regulation of these genes is not unique to NGF. Because each of these genes was expressed in response to phorbol myristate acetate and EGF, their expression may be necessary but is certainly not sufficient for neurite formation. The protein kinase inhibitor K-252a prevented the NGF-associated, but not the acidic FGF-associated, induction of d-2 and d-5 gene expression, suggesting that these two growth factors may regulate gene expression via different cellular pathways. The study of the regulation of the expression of these and other NGF-inducible genes should valuable new information concerning how NGF and other growth factors cause neural differentiation.

MeSH Terms
Animals Blotting, Northern Bucladesine Cholera Toxin/pharmacology Cloning, Molecular Epidermal Growth Factor/physiology Fibroblast Growth Factors/physiology Gene Expression Regulation Genes, Regulator Insulin/physiology Nerve Growth Factors/genetics,physiology Rats Second Messenger Systems Tetradecanoylphorbol Acetate/pharmacology Transcription, Genetic Tumor Cells, Cultured
Chemicals
Insulin Nerve Growth Factors Fibroblast Growth Factors Epidermal Growth Factor Bucladesine Cholera Toxin Tetradecanoylphorbol Acetate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cho K O
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
Skarnes W C
Minsk B
Palmieri S
Jackson-Grusby L
Wagner J A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.9.1.135-143.1989
Published
1989-01-00
Pages
135-43
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC362154
Subset
IM
Grants
NCI NIH HHS · CA22427 · United States
NCRR NIH HHS · RR05526-22 · United States
External Links
PubMed source DOI: 10.1128/mcb.9.1.135-143.1989 PMC Full Text View journal details
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