@entity28888 and PHAS-II are members of a newly discovered family of proteins that regulate translation initiation. @entity28888 is expressed in a wide variety of cell types, but it is highest in adipocytes, where protein synthesis is markedly increased by insulin. PHAS-II is highest in liver and kidney, where very little @entity28888 is found. PHAS proteins bind to @entity3801 , the mRNA cap-binding protein, and inhibit translation of capped mRNA in vitro and in cells. In @entity35 adipocytes @entity28888 is phosphorylated in at least five sites, all of which conform to the consensus, (Ser/Thr)-Pro. Both PHAS proteins are phosphorylated in response to insulin or growth factors, such as EGF, PDGF and @entity2135 . Phosphorylation in the appropriate site(s) promotes dissociation of PHAS/ @entity3801 complexes. This allows @entity3801 to bind to @entity44031 ( @entity66054 ), thereby increasing the amount of the eIF-4F complex and the rate of translation initiation. Increasing @entity268 promotes @entity28888 dephosphorylation and increases binding to @entity3801 . Unlike @entity28888 , PHAS-II is readily phosphorylated by PKA in vitro, suggesting that regulation of the two proteins differs. However, increasing @entity268 in cells also promotes dephosphorylation of PHAS-II. Thus, PHAS proteins appear to be key mediators not only of the stimulatory effects of insulin and growth factors on protein synthesis, but also of the inhibitory effects of @entity268 . Moreover, by controlling @entity3801 PHAS proteins may be involved in the control of cell proliferation, as increasing @entity3801 is mitogenic and can even cause malignant transformation of cells. MAP kinase readily phosphorylates both @entity28888 and PHAS-II in vitro, but inhibiting activation of MAP kinase does not attenuate the effects of insulin on increasing phosphorylation of the PHAS proteins in adipocytes or skeletal muscle. MAP kinase phosphorylates neither @entity28888 nor PHAS-II at a significant rate when the proteins are bound to @entity3801 . Therefore, the role of MAP kinase in promoting the dissociation of PHAS/ @entity3801 complexes is not clear. Of several protein kinases tested, only casein kinase-II phosphorylated @entity28888 when it was bound @entity3801 . Indeed, the bound form of @entity28888 was phosphorylated more rapidly than the free form. However, it is unlikely that casein kinase II regulates either PHAS protein, as the major site (Ser111) in @entity28888 phosphorylated by casein kinase II in vitro is not phosphorylated in adipocytes, and PHAS-II is not a substrate for casein kinase-II. Pharmacological and genetic evidence indicates that the @entity3470 / @entity14446 pathway is involved in the control of @entity28888 . Thus, PHAS proteins may be mediators of the effects of this pathway on protein synthesis and cell proliferation.

PHAS proteins as mediators of the actions of insulin, growth factors and XXXX on protein synthesis and cell proliferation.

@entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity3801 :: ('117045(Tax:10116)', 'Gene') :: ['eIF-4E'] @entity66054 :: ('296211(Tax:10116)', 'Gene') :: ['p220'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity2135 :: ('24482(Tax:10116)', 'Gene') :: ['IGF-1'] @entity44031 :: ('287986(Tax:10116)', 'Gene') :: ['eIF-4G'] @entity28888 :: ('116636(Tax:10116)', 'Gene') :: ['PHAS-I and -II', 'PHAS-I'] @entity14446 :: ('83840(Tax:10116)', 'Gene') :: ['p70S6K']
@entity268 :: (CHEBI:17489,Chemical) :: ['cAMP']
