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

C. M. Machida, J. D. Scott, Gary Ciment

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 neurite 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.

Original languageEnglish (US)
Pages (from-to)1037-1048
Number of pages12
JournalJournal of Cell Biology
Volume114
Issue number5
StatePublished - 1991

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Matrix Metalloproteinase 3
PC12 Cells
Metalloproteases
Nerve Growth Factor
Protein Kinases
Staurosporine
Phosphotransferases
Messenger RNA
Immediate-Early Genes
Protein-Serine-Threonine Kinases
Staphylococcal Protein A
Neurites
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Protein Kinase C
Genes

ASJC Scopus subject areas

  • Cell Biology

Cite this

NGF-induction of the metalloproteinase transin/stromelysin in PC12 cells : Involvement of multiple protein kinases. / Machida, C. M.; Scott, J. D.; Ciment, Gary.

In: Journal of Cell Biology, Vol. 114, No. 5, 1991, p. 1037-1048.

Research output: Contribution to journalArticle

Machida, C. M. ; Scott, J. D. ; Ciment, Gary. / NGF-induction of the metalloproteinase transin/stromelysin in PC12 cells : Involvement of multiple protein kinases. In: Journal of Cell Biology. 1991 ; Vol. 114, No. 5. pp. 1037-1048.
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