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• W2085765983 abstract "The synergism between insulin and prolactin (PRL) in their effect on protein synthesis in the mammary gland was studied in differentiating mammary epithelial CID-9 cells. Both hormones were needed to induce phosphorylation of PHAS-I which resulted in its dissociation from the eIF-4E translation initiation factor. This step is crucial for the initiation of translation. The induction of PHAS-I phosphorylation was rapid and its rate matched that demonstrated for the JAK2/STAT5a and the binding of STAT5a to its DNA binding motif. However, 120 min was needed for complete phosphorylation of the PHAS-I protein. In the presence of insulin, PRL induced MAP kinase activity, initiated at a comparable rate to that of PHAS-I phosphorylation. However, a line of evidence suggested that although this kinase phosphorylates PHAS-I in vitro, it does not actively participate in its phosphorylation in vivo: (a) the level of insulin needed to enable PRL-induced ERK-1/ERK-2 activation was one order of magnitude higher than that needed for PHAS-I phosphorylation; and (b) PD 098059, a MEK-1 inhibitor, completely inhibited insulin-dependent, PRL-induced ERK-1/ERK-2 activation but had no effect on the PRL-induced PHAS-I phosphorylation. In contrast, wortmannin, a phosphatidylinositol 3-kinase (PI 3′-kinase) inhibitor and the immunosuppressant rapamycin abrogated PHAS-I phosphorylation and caused a reciprocal shift between the fully phosphorylated PHAS-I γ form and its non-phosphorylated α form. Since the partly phosphorylated PHAS-I β form was not significantly affected by these inhibitors, it is possible that more than a single kinase mediates the synergistic effect of prolactin and insulin on PHAS-I phosphorylation." @default.
• W2085765983 created "2016-06-24" @default.
• W2085765983 creator A5014833287 @default.
• W2085765983 date "1999-09-01" @default.
• W2085765983 modified "2023-10-11" @default.
• W2085765983 title "Prolactin and insulin synergize to regulate the translation modulator PHAS-I via mitogen-activated protein kinase-independent but wortmannin- and rapamycin-sensitive pathway" @default.
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• W2085765983 doi "https://doi.org/10.1016/s0303-7207(99)00116-1" @default.
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