Prolactin-releasing peptide activation of the prolactin promoter is differentially mediated by extracellular signal-regulated protein kinase and c-Jun N-terminal protein kinase
A. Kimura et al., Prolactin-releasing peptide activation of the prolactin promoter is differentially mediated by extracellular signal-regulated protein kinase and c-Jun N-terminal protein kinase, J BIOL CHEM, 275(5), 2000, pp. 3667-3674
Regulation of the mitogen-activated protein kinase (MAPK) family by prolact
in-releasing peptide (PrRP) in both GH3 rat pituitary tumor cells and prima
ry cultures of rat anterior pituitary cells was investigated. PrRP rapidly
and transiently activated extracellular signal-regulated protein kinase (ER
K) in both types of cells. Both pertussis toxin, which inactivates G(i)/G(o
), proteins, and exogenous expression of a peptide derived from the carboxy
l terminus of the beta-adrenergic receptor kinase I, which specifically blo
cks signaling mediated by the beta gamma subunits of G proteins, completely
blocked the PrRP-induced ERK activation, suggesting the involvement of G(i
)/G(o) proteins in the PrRP-induced ERK activation, Down-regulation of cell
ular protein kinase C did not significantly inhibit the PrRP-induced ERK ac
tivation, suggesting that a protein kinase C-independent pathway is mainly
involved. PrRP-induced ERK activation was not dependent on either extracell
ular Ca2+ or intracellular Ca2+. However, the ERK cascade was not the only
route by which PrRP communicated with the nucleus, JNK was also shown to be
significantly activated in response to PrRP, JNK activation in response to
PrRP was slower than ERK activation, Moreover, to determine whether a MAPK
family cascade regulates rat prolactin (rPRL) promoter activity, we transf
ected the intact rPRL promoter ligated to the firefly luciferase reporter g
ene into GH3 cells. PrRP activated the rPRL promoter activity in a time-dep
endent manner. Co-transfection with a catalytically inactive form of a MAPK
construct or a dominant negative JNK, partially but significantly inhibite
d the induction of the rPRL promoter by PrRP, Furthermore, co-transfection
with a dominant negative Ets completely abolished the response of the rPRL
promoter to PrRP, These results suggest that PrRP differentially activates
ERK and JNK, and both cascades are necessary to elicit rPRL promoter activi
ty in an Ets-dependent mechanism.