Bd. Mazer et al., ROLE FOR CA2-CYCLE-REGULATED GENES IN PAF-STIMULATED CELLS( IN EXPRESSION OF CELL), Journal of lipid mediators and cell signalling, 10(3), 1994, pp. 269-281
Platelet-activating factor (PAF) is a powerful stimulator of a wide va
riety of cells. In transformed human B-lymphoblastoid cell lines, PAF
increases intracellular Ca2+ concentrations ([Ca2+](i)) and induces th
e expression of the proto-oncogenes c-fos and early growth response ge
ne-2 (EGR2). Here, we present data that evaluates the role of Ca2+ in
the PAF-dependent induction of these cell-cycle activated genes. PAF (
10(-7) M) increased c-fos and EGR2 mRNA levels in cells suspended in C
a2+-containing medium by 6-10-fold. In PAF-stimulated cells suspended
in medium depleted of Ca2+, eliminating Ca2+ influx but not intracellu
lar store release of Ca2+, the induction of gene expression was reduce
d by approx. 50%. In contrast, buffering of Ca2+ released from intrace
llular stores but maintaining transmembrane Ca2+ uptake had little eff
ect on gene expression. When both sources of Ca2+ were eliminated, PAF
-stimulated expression of these genes was completely prevented. This w
as not due to any toxicity to the cells since the response to phorbol
ester under identical conditions was unaffected. The regulation of c-f
os mRNA expression was paralleled by changes in levels of FOS protein.
These data indicate that changes in [Ca2+](i), primarily from stimula
ted entry across the plasma membrane and to a lesser extent release of
Ca2+ from sequestered intracellular stores, play an essential role in
PAF-dependent triggering of c-fos and EGR2 mRNA expression.