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Induction of the collagenase phorbol ester response element by staurosporine
Author(s) -
Shoshan Maria C.,
Linder Stig
Publication year - 1994
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240550409
Subject(s) - staurosporine , protein kinase c , collagenase , protein kinase a , phorbol , microbiology and biotechnology , messenger rna , protein kinase inhibitor , kinase , biology , chemistry , biochemistry , enzyme , gene
The indol alkaloid staurosporine is a potent inhibitor of protein kinase C, but has also been shown to have certain effects paradoxically similar to those of protein kinase C–activating phorbol esters. We show here that collagenase mRNA expression is stimulated by 10 nM staurosporine in normal and ras ‐oncogene–transformed rat fibroblasts. The kinetics of collagenase mRNA induction by staurosporine were slow compared to induction by phorbol ester. Staurosporine induction of the collagenase promoter appeared to be mediated via the TPA response element (TRE). Induction did not involve any increase in jun mRNA expression and did not require expression of c‐Jun. Prolonged treatment with phorbol ester to deplete protein kinase C did not inhibit stimulation of the collagenase promoter by staurosporine. Instead, involvement of cAMP‐dependent protein kinase (PKA) was indicated by inhibition of staurosporine induction by the PKA inhibitor H‐89. In addition, raised levels of cAMP were observed during the first hour of staurosporine treatment. Altogether, our data indicate that staurosporine induces a PKA‐dependent pathway leading to c‐Jun–independent activation of the collagenase TRE element. © 1994 Wiley‐Liss, Inc.