Premium
Down‐regulation of the protein kinase A pathway by activators of protein kinase C and intracellular Ca 2+ in fibroblast cells
Author(s) -
Döbbeling Udo,
Berchtold Martin W.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00748-x
Subject(s) - protein kinase a , intracellular , chemistry , microbiology and biotechnology , protein kinase c , c raf , ask1 , mitogen activated protein kinase kinase , kinase , cyclin dependent kinase 2 , map kinase kinase kinase , fibroblast , biochemistry , biology , in vitro
Many genese are regulated by the intracellular calcium protein kinase C (PKC) and protein kinase A (PKA) pathways and it has been shown that these pathways synergize in some cell types, whereas they antagonize in others. Here we show that the calcium and PKC pathways suppress the effects mediated by the PKA pathway in a fibroblast cell line. The suppressing effect of elevated intracellular Ca 2+ levels, but not of the PKC pathway, can be abrogated by the addition of cyclosporin A (CsA), indicating that the effect of Ca 2+ is mediated by phosphatase‐2B (PP‐2B/calcineurin). Suppression by the PKC pathway is not mediated by the proto‐oncogenes c‐ fos , c‐ jun and jun B, as the co‐transfection of these genes does not block the effects of the PKA stimulator 8‐Br‐cAMP. In addition, cotransfection with the catalytic subunit of PKA shows that the inhibitory effect of PKC occurs upstream of PKA activation.