Previous work has shown that naturally phosphorylated @entity20514 antagonizes the growth-promoting activities of unmodified @entity20514 (U-PRL) and that this effect is duplicated by a molecular mimic, @entity70286 PRL. At the same time, the @entity70286 PRL is a superagonist with regard to expression of some PRL-regulated genes. We have asked whether the different activities of U-PRL and @entity70286 PRL are the result of differential signaling. HC11 cells (a normal @entity19 mammary cell line) were grown to confluence, primed with @entity701 , and then exposed to the PRLs. A 15 min incubation of PRL-naive cells led to substantial @entity669 phosphorylation of @entity16404 and @entity23117 by U-PRL and an essentially equivalent @entity16404 activation by @entity70286 PRL. The latter, however, was accompanied by reduced @entity669 phosphorylation of @entity23117 . EMSA analysis using a Stat 5 binding site showed both PRLs to cause equivalent binding of nuclear proteins and that most of what bound was complexed through @entity23117 . @entity13269 analysis of Stat 5 showed @entity70286 PRL to double the amount of @entity563 phosphorylation versus that seen with U-PRL. Analysis of the MAP kinase pathway showed U-PRL capable of activation of @entity8837 but that signaling via @entity8837 was greater with @entity70286 PRL. A 7-day incubation in either PRL increased beta-casein mRNA levels, but @entity70286 PRL caused a 2-fold increase over that seen with U-PRL. The increase, over that seen with U-PRL, was blocked by the MAP kinase inhibitor, @entity4286 . After 7 days of treatment with @entity70286 PRL, expression of the short PRL receptor was doubled, and signaling showed a greater dependence on the MAP kinase pathway (2.9-fold increase in @entity8837 activation). We conclude that although both PRLs use both pathways to some extent, U-PRL signals primarily through @entity16404 -Stat 5 whereas @entity70286 PRL signals primarily through the MAP kinase pathway especially after prolonged exposure. This is the first demonstration of differential involvement of signaling pathways by different forms of PRL.

Different biological effects of unmodified XXXX and a molecular mimic of phosphorylated @entity20514 involve different signaling pathways.

@entity16404 :: ('16452(Tax:10090)', 'Gene') :: ['Jak 2'] @entity23117 :: ('20850(Tax:10090)', 'Gene') :: ['Stat 5a'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity20514 :: ('19109(Tax:10090)', 'Gene') :: ['prolactin'] @entity13269 :: ('CHEBI:26051', 'Chemical') :: ['Phosphoamino acid'] @entity701 :: ('MESH:D006854', 'Chemical') :: ['hydrocortisone'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD98059'] @entity70286 :: ('p|SUB|S|179|D', 'ProteinMutation') :: ['S179D'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity8837 :: ('26417;26413', 'Gene') :: ['ERK 1 and 2', 'ERKs 1 and 2']
@entity20514 :: (19109(Tax:10090),Gene) :: ['prolactin']
