Basic fibroblast growth factor (bFGF) regulation of the plasma membrane calcium ATPase (PMCA) as part of an anti-apoptotic mechanism of action.
Basic fibroblast growth factor (bFGF) preserves the viability of at least 13 different cells, including epithelial, endothelial, smooth muscle and neuronal cells. In spite of this profound and rather universal effect on cell viability, detailed studies regarding the mechanism of bFGF's action have not been conducted. Rather, most studies have simply shown that bFGF inhibits cells from undergoing programmed cell death (i.e. apoptosis). The most mechanistic studies to date have been conducted on either neurons or ovarian (granulosa) cells. These studies have shown that bFGF prevents apoptosis through both genomic and acute actions. Basic FGF's acute actions involved the maintenance of normal levels of intracellular free calcium levels ([Ca(2+)](i)). In granulosa cells, bFGF maintained [Ca(2+)](i) through a protein kinase C(delta) (PKCdelta)-dependent mechanism. Further, bFGF-activated PKCdelta maintained [Ca(2+)](i) by stimulating calcium efflux. The ability of bFGF to stimulate calcium efflux involved the plasma membrane calcium ATPase (PMCA). Interestingly, bFGF-activated PKCdelta appeared to regulate PMCA activity in part by promoting its membrane localization.
Peluso
John J
JJ
Department of Physiology, University of Connecticut Health Center, Farmington, CT 06030, USA. peluso@nos2.uchc.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D027682:Cation Transport Proteins; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006107:Granulosa Cells / Q000166:cytology; D006801:Humans; D010053:Ovary / Q000166:cytology*; D053499:Plasma Membrane Calcium-Transporting ATPases; D011493:Protein Kinase C / Q000502:physiology; D051745:Protein Kinase C-delta
D027682:Cation Transport Proteins; D016222:Fibroblast Growth Factor 2; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases