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PMID: 1908468 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

NGF-induction of the metalloproteinase-transin/stromelysin in PC12 cells: involvement of multiple protein kinases.

The Journal of cell biology ·Vol. 114 ·No. 5 ·1991-09-00 ·Pages 1037-48

Machida CM, Scott JD, Ciment G

Abstract

In previous work, we found that nerve growth factor (NGF) induced expression of the mRNA transcript encoding the metalloproteinase transin/stromelysin in PC12 cells. Transin was found, moreover, to be a "late" gene product whose expression correlated with neurites extension. In this study, various aspects of the NGF intracellular signaling pathway in PC12 cells are investigated. We show that the protein kinase inhibitor staurosporine, but not various other kinase inhibitors, specifically blocked the NGF induction of transin. Preliminary characterization of this staurosporine-sensitive kinase suggest that it does not correspond to a tyrosine kinase, nor various serine kinases, and that it is involved both at the transcriptional and posttranscriptional levels of transin gene regulation. In contrast to these effects of staurosporine, various activators of protein kinases C and A augmented the NGF induction of transin. Similar effects of these kinase inhibitors and activators were also observed with the expression of various immediate-early genes that have been proposed to mediate the transcriptional effects of NGF, including c-fos and c-jun. These data suggest, therefore, that the NGF induction of transin mRNA expression involves multiple protein kinases acting at a number of postreceptor regulatory steps in the NGF signaling pathway.

MeSH Terms
Adrenal Gland Neoplasms Alkaloids/pharmacology Animals Blotting, Northern Cell Differentiation/drug effects Cell Nucleus/physiology DNA-Binding Proteins/genetics Enzyme Activation/drug effects Enzyme Induction/drug effects Gene Expression Regulation/drug effects In Vitro Techniques Intermediate Filament Proteins/genetics Matrix Metalloproteinase 3 Metalloendopeptidases/metabolism Nerve Growth Factors/pharmacology Neurofilament Proteins Pheochromocytoma Protein Kinase C/physiology Protein Kinase Inhibitors Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun RNA, Messenger/genetics Rats Staurosporine Tetradecanoylphorbol Acetate/pharmacology Transcription Factors/genetics Tumor Cells, Cultured
Chemicals
Alkaloids DNA-Binding Proteins Intermediate Filament Proteins Nerve Growth Factors Neurofilament Proteins Protein Kinase Inhibitors Proto-Oncogene Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun RNA, Messenger Transcription Factors Protein Kinase C Metalloendopeptidases Matrix Metalloproteinase 3 Staurosporine Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Machida C M
Department of Cell Biology and Anatomy, Oregon Health Sciences University, Portland 97201-3098.
Scott J D
Ciment G
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.114.5.1037
Published
1991-09-00
Pages
1037-48
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2289118
Subset
IM
Grants
NIGMS NIH HHS · GM44427 · United States
NINDS NIH HHS · NS23886 · United States
External Links
PubMed source DOI: 10.1083/jcb.114.5.1037 PMC Full Text View journal details
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