MAPK regulates cyclin D1 but not cyclin E levels in the 5-HT2B receptor
mitogenic signaling and is regulated by tyrosine kinases.
(A) Depletion of MAPK by antisense transfection. LM6
cells were transfected transiently with antisense (AS) or sense (S)
oligonucleotides of mouse MAPK (ERK1/2) mRNA and probed with
MAPK antibody. (B) 5-HT-induced cyclin D1 expression,
but not that of cyclin E, is abolished in MAPK-depleted cells. After
visualization with anti-cyclin D1 antibody, the membranes were washed
and reprobed with cyclin E antibody. The positions of cyclin E and
cyclin D1 are indicated. (C) MAPK activation is
regulated by tyrosine kinases. After pretreatment with inhibitors for
MAPK kinase (15 μM PD 098059), tyrosine kinase (15 μM genistein),
Src (1 μM PP1), and PDGFR (0.1 μM AG 1296), the cells were
incubated with 5-HT (1 μM) for 10 min, then revealed with anti-active
MAPK antibody. After being revealed by enhanced chemiluminescence, the
relative active ERK1 and ERK2 protein levels were assessed by using a
luminometer. The stars indicate significant inhibition of the
parameters as compared with 5-HT stimulation alone
(P < 0.05; n > 3).