Insulin and Prolactin Synergistically Stimulate β-Casein Messenger Ribonucleic Acid Translation by Cytoplasmic Polyadenylation
| Autor: | Itamar Barash, Kyoung Moo Choi, Robert E. Rhoads |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cytoplasm
Polyadenylation medicine.medical_treatment Cytoplasmic polyadenylation element Cell Cycle Proteins DNA-Directed DNA Polymerase Biology Mice Mammary Glands Animal Endocrinology Polysome Protein biosynthesis medicine Animals Insulin RNA Messenger Eukaryotic Initiation Factors 3' Untranslated Regions Molecular Biology Cells Cultured Adaptor Proteins Signal Transducing Messenger RNA Three prime untranslated region Caseins RNA-Binding Proteins Drug Synergism Epithelial Cells General Medicine Milk Proteins Phosphoproteins Molecular biology Prolactin Polyribosomes Protein Biosynthesis Female Carrier Proteins Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) Signal Transduction |
| Zdroj: | Molecular Endocrinology. 18:1670-1686 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Previous studies have shown that the synthesis and stability of milk protein mRNAs are regulated by lactogenic hormones. We demonstrate here in cultured mouse mammary epithelial cells (CID 9) that insulin plus prolactin also synergistically increases the rate of milk protein mRNA translation. Insulin alone stimulates synthesis of both milk and nonmilk proteins, whereas prolactin alone has no effect, but insulin plus prolactin selectively stimulate synthesis of milk proteins more than insulin alone. The increase in beta-casein mRNA translation is also reflected in a shift to larger polysomes, indicating an effect on translational initiation. Inhibitors of the phosphatidylinositol 3-kinase, mammalian target of rapamycin, and MAPK pathways block insulin-stimulated total protein and beta-casein synthesis but not the synergistic stimulation. Conversely, cordycepin abolishes synergistic stimulation of protein synthesis without affecting insulin-stimulated translation. The poly(A) tract of beta-casein mRNA progressively increases from approximately 20 to about 200 A residues over 30 min of treatment with insulin plus prolactin. The 3'-untranslated region of beta-casein mRNA containing an unaltered cytoplasmic polyadenylation element is sufficient for the translational enhancement and mRNA-specific polyadenylation, based on transient transfection of cells with a reporter construct. Insulin and prolactin stimulate cytoplasmic polyadenylation element binding protein phosphorylation with no increase of cytoplasmic poly(A) polymerase activity. |
| Databáze: | OpenAIRE |
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