Fibroblast growth factor stimulates protein kinase C in quiescent 3T3 cells without Ca²⁺ mobilization or inositol phosphate accumulation

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 Ca2+ 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 [Ca2+], 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 Ca2+ mobilization.

The Proliferative Effect of Vascular Endothelial Growth Factor Requires Protein Kinase C-α and Protein Kinase C-ζ

“…Possibly, sphingomyelin hydrolysis and the generation of ceramide play a role in the signal transduction of VEGF receptors. 28 Similar observations have been made by Nanberg et al 29 for another endothelial cell growth factor which binds to a tyrosine kinase receptor, namely FGF. They hypothesized that bFGF stimulates PKC through a signal transduction pathway distinct from inositol phospholipid turnover.…”

“…They hypothesized that bFGF stimulates PKC through a signal transduction pathway distinct from inositol phospholipid turnover. However, Nanberg et al 29 ] i signal. We observed a stimulatory effect of VEGF on PKC isoforms ␣ and .…”

Modulation of Gingival Fibroblast Minocycline Accumulation by Biological Mediators

“…The mechanism of enhancement (increased transporter affinity) and the magnitude of the enhancement are similar to those produced by PDGF, FGF-2, TGF-β, and TNF-α. All 4 of these mediators activate a complex cascade of fibroblast signaling pathways, but some of their effects are exerted through activation of PKC (Nanberg et al, 1990;Gorospe et al, 1993;Axmann et al, 1998;Thorsen et al, 2003).…”

Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor.

“…For example, bFGF can also activate protein kinase C (PKC) through PLCy-independent pathways (55,56). PKC, in turn, can potentiate the actions of CamKinase II by increasing the availability of cytosolic calmodulin (57,58).…”