Premium
Fibroblast growth factor stimulates protein kinase C in quiescent 3T3 cells without Ca 2+ mobilization or inositol phosphate accumulation
Author(s) -
Nånberg Eewa,
Morris Clive,
Higgins Theresa,
Vara Francisco,
Rozengurt Enrique
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041430206
Subject(s) - protein kinase c , basic fibroblast growth factor , biology , protein kinase a , inositol , epidermal growth factor , phospholipase c , diacylglycerol kinase , signal transduction , inositol phosphate , fibroblast growth factor , microbiology and biotechnology , kinase , growth factor , biochemistry , receptor
Abstract To elucidate the transmembrane signalling processes initiated by fibroblast growth factor (FGF), we have studied the effect of recombinant basic FGF (bFGF) on various early events associated with mitogenesis in Swiss 3T3 fibroblasts. bFGF, at mitogenic concentrations, neither induced Ca 2+ mobilization from intracellular stores nor increased the accumulation of inositol phosphates. In contrast, bFGF stimulated the phosphorylation of the Mr 80,000 (80K) cellular protein which is a major substrate of protein kinase C. This effect was potentiated by the diacylglycerol kinase inhibitor R59022. Two‐dimensional polyacrylamide gel electrophoresis and phosphopeptide mapping showed that the 80K phosphoproteins generated in response to bFGF, bombesin, and phorbol 12,13‐dibutyrate were indistinguishable. Down‐regulation of protein kinase C prevented bFGF stimulation of 80K phosphorylation. Other protein kinase C‐dependent early events such as transmodulation of the epidermal growth factor receptor, cytoplasmic alkalinization, inhibition of vasopressin induced increase in cytosolic [Ca 2+ ], and enhancement of cAMP accumulation in response to forskolin were also induced by bFGF. Similar results were obtained when bFGF was added to quiescent cultures of tertiary mouse embryo fibroblasts. We conclude that bFGF stimulates protein kinase C through a signal transduction pathway distinct from inositol phospholipid turnover and Ca 2+ mobilization.