E. Chaikin et al., ENHANCEMENT OF INTERLEUKIN-3-DEPENDENT MAST-CELL PROLIFERATION BY SUPPRESSION OF C-JUN EXPRESSION, The Journal of biological chemistry, 269(11), 1994, pp. 8498-8503
We have previously shown that protein kinase C (PKC) depletion is asso
ciated with an increase in the proliferation of interleukin 3 (IL-3)-i
nduced mast cells. Here we show that the AP-1 components c-Jun and c-F
os are induced by IL-3. While c-Jun's induction by IL-3 is totally dep
endent on PKC, c-Fos induction by IL-3 is only attenuated by PKC deple
tion. AP-1 binding activity was also induced by IL-3 but this inductio
n was PKC independent. These results indicated a possible involvement
of c-Jun in the inhibition of IL-3-induced growth regulation. A suppor
t for this assumption came from experiments in which an increase in th
ymidine incorporation into mast cells was noted when c-jun antisense o
ligomers were administered to IL-3-treated cells. Since the only known
effect of direct inhibition of c-Jun on proliferation rates in severa
l cellular systems was a reduction of proliferation, we verified that
our c-jun antisense oligomer could also inhibit proliferation rates in
fibroblasts where such a repression was previously reported. Thus c-J
un has an inhibitory effect on IL-3 induction of mast cells proliferat
ion that is distinct from its role in several other cellular environme
nts. These observations reveal the involvement of AP-1 and its compone
nts in IL-3-induced signal transduction and the importance of the mast
cell environment in determining their specific cellular function.