Bailie et al. [In Vitro Cell Dev. Biol. (1992) 28A, 621-624] reported that primary cultures of @entity35 hepatocytes possess low affinity binding sites for @entity2137 ( @entity2137 ). @entity2137 treatment of primary cultures of @entity35 hepatocytes with a maximally effective concentration of @entity2137 (20 ng/ml, 0.8 nM) caused acute phasic activation of @entity18945 and p42(MAPkinase), and a smaller sustained activation of @entity45100 . The transient increase in @entity18945 and p42(MAPkinase) activity returned to baseline within approximately 30 min. @entity2137 treatment of hepatocytes did not induce expression of cyclin dependent kinase (cdk) inhibitor proteins, but instead stimulated @entity23305 activity and increased @entity665 incorporation into DNA. In contrast to hepatocytes, @entity2137 treatment of PC12 @entity1911 cells caused large sustained activations of @entity45100 and p42(MAPkinase), and a lower phasic activation of @entity18945 . The sustained activations of @entity45100 and p42(MAPkinase) were for more than 5 h. Treatment of PC12 cells with @entity2137 increased @entity7504 ( @entity9533 / @entity9533 ) expression, reduced @entity23305 activity and inhibited DNA synthesis, the opposite to the effects of @entity2137 treatment of hepatocytes. However when p42(MAPkinase) was chronically activated in hepatocytes, via @entity281 with an inducible @entity2931 receptor- @entity18945 fusion protein, expression of @entity7504 ( @entity9533 / @entity9533 ) and @entity11754 ( @entity11754 ) cdk inhibitor proteins increased, @entity23305 activity decreased, and DNA synthesis decreased. Equally, treatment of hepatocytes with 50 mM @entity1068 elevated the basal activity of p42(MAPkinase) and temporally extended the ability of @entity2137 treatment to activate p42(MAPkinase). @entity1068 and @entity2137 co-treatment increased expression of @entity7504 ( @entity9533 / @entity9533 ) and @entity11754 ( @entity11754 ) cdk inhibitor proteins and decreased hepatocyte DNA synthesis. These data demonstrate that @entity2137 can cause either acute/phasic or sustained activation of the @entity3457 kinase cascade in different cell types. Acute activation of the @entity3457 kinase cascade correlated with increased DNA synthesis. In contrast, sustained activation of the @entity3457 kinase cascade correlated with increased expression of cdk inhibitor proteins, a reduction in cdk activity, and an inhibition of DNA synthesis. These data suggest a general mechanism exists where acute activation of the @entity3457 kinase cascade promotes G1 progression/S phase entry and that chronic activation of the @entity3457 kinase cascade inhibits this process.

The @entity3457 ( XXXX ) kinase cascade can either stimulate or inhibit DNA synthesis in primary cultures of @entity35 hepatocytes depending upon whether its activation is acute/phasic or chronic.

@entity7504 :: ('24525(Tax:10116)', 'Gene') :: ['p21'] @entity45100 :: ('114486(Tax:10116)', 'Gene') :: ['B-Raf'] @entity2137 :: ('310738(Tax:10116)', 'Gene') :: ['NGF', 'nerve growth factor'] @entity18945 :: ('24703(Tax:10116)', 'Gene') :: ['Raf-1'] @entity1911 :: ('MESH:D010673', 'Disease') :: ['pheochromocytoma'] @entity2931 :: ('CHEBI:50114', 'Chemical') :: ['oestrogen'] @entity11754 :: ('25163(Tax:10116)', 'Gene') :: ['INK4a', 'p16'] @entity9533 :: ('114851(Tax:10116)', 'Gene') :: ['WAF1', 'WAF-1', 'Cip1', 'Cip-1'] @entity665 :: ('CHEBI:53526', 'Chemical') :: ['[3H]thymidine'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['Ethanol', 'ethanol'] @entity3457 :: ('OMIM:612348', 'Disease') :: ['MAP'] @entity23305 :: ('362817(Tax:10116)', 'Gene') :: ['cdk2']
@entity3457 :: (OMIM:612348,Disease) :: ['MAP']
