V. Mitev et al., THE EFFECT OF PROLACTIN ON CASEIN KINASE-II, MAP KINASE AND PKC IN RABBIT MAMMARY CELLS AND NB-2 RAT LYMPHOID-CELLS, Biochemical pharmacology, 52(11), 1996, pp. 1719-1727
Prolactin induces milk protein gene expression in rabbit primary mamma
ry cells without any concomitant cell multiplication. Prolactin or oth
er lactogenic hormones is the major inducer of cell division in the ra
t lymphoid Nb-2 cells. In Nb-2 cells, prolactin also rapidly induces t
he expression of the c-myc gene, and beta-actin and stathmin gene expr
ession is induced more slowly. The possible involvement of casein kina
se II (CKII), mitogen-activated protein kinase (MAPK) and protein kina
se C (PKC) in these process is not well known. The present work was un
dertaken to evaluate the effect of prolactin on these protein kinases
and to determine the possible involvement of these enzymes in the acti
vity of several genes under the control of the hormone. In rabbit mamm
ary cells, prolactin did not alter CKII activity but did transiently s
timulate MAP kinase activity. Prolactin also stimulated Ca2+-independe
nt PKC. This effect was visible after 10 min and was maintained for at
least 24 hr. Staurosporine, an inhibitor of PKC and of several tyrosi
ne kinases altered Ca2+-independent PKC only moderately. In contrast,
GF 109203X, a potent and specific inhibitor of PKC, abrogated almost a
ll PKC activity. Staurosporine, but not GF 109203X, prevented the indu
ction of the casein gene by prolactin. In Nb-2 cells, prolactin induce
d a slow stimulation of CKII activity. The hormone did not induce MAP
kinase activity. Prolactin stimulated Ca2+-independent PKC over period
s of 24 hr. GF 109203X, but not staurosporine, inhibited PKC activity,
whereas staurosporine but not GF 109203X, inhibited the induction of
Nb-2 cell multiplication and the accumulation of c-myc, beta-actin and
stathmin mRNAs. From these data, it can be concluded that (1) the sti
mulation of CKII by prolactin in Nb-2 cells is concomitant with cell m
ultiplication: (2) MAPK stimulation is not necessary for prolactin to
induce Nb-2 cell multiplication; and (3) PKC is stimulated in mammary
and Nb-2 cells, but this stimulation is not required for prolactin to
stimulate casein, c-myc, beta-actin and stathmin gene expression and N
b-2 cell division. (C) 1996 by Elsevier Science Inc.