Insulin and cyclic adenosine monophosphate increase prolactin gene expression through different response pathways
Autor: | Frederick M. Stanley, Kirsten K. Jacob |
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Rok vydání: | 1995 |
Předmět: |
medicine.medical_specialty
Recombinant Fusion Proteins medicine.medical_treatment Phosphodiesterase 3 Second Messenger Systems Biochemistry chemistry.chemical_compound Endocrinology Genes Reporter Internal medicine Insulin receptor substrate Cyclic AMP Tumor Cells Cultured medicine Animals Insulin Pituitary Neoplasms Cyclic adenosine monophosphate Promoter Regions Genetic Molecular Biology Dose-Response Relationship Drug biology Chemistry Cyclic AMP-Dependent Protein Kinases Prolactin Rats Enzyme Activation Insulin receptor Electroporation Gene Expression Regulation Regulatory sequence Calcium-Calmodulin-Dependent Protein Kinases biology.protein PDE10A CREB1 |
Zdroj: | Molecular and Cellular Endocrinology. 109:175-181 |
ISSN: | 0303-7207 |
DOI: | 10.1016/0303-7207(95)03500-7 |
Popis: | Insulin and cAMP stimulate prolactin gene transcription and prolactin-CAT expression in rat pituitary tumor GH cells. Expression of prolactin-CAT construct, pPrl(−173/+75)CAT, is stimulated 10- to 30-fold by either insulin or cAMP Addition of both insulin and cAMP resulted in an additive 20- to 60-fold stimulation. Although the regulatory sequences have not been defined precisely, both insulin and CAMP appear to stimulate transcription of prolactin-CAT expression through possibly identical sequences in the −106 −87 region of the promoter. Insulin mediated increases in prolactin-CAT expression are not ras-dependent in GH4 cells. Thus, a number of experiments were performed to determine that the effects of insulin and CAMP are independent. First, insulin does not stimulate cAMP levels in GH4 cells. Second, CAMP action was inhibited by expression of a mutant regulatory subunit of cAMP-dependent protein kinase A that does not bind CAMP and by expression of an inhibitor of cAMP-dependent protein kinase A, while insulin action was not affected by expression of these proteins. Thus, although the regulatory sequences for insulin and CAMP may be identical, the effects of insulin and cAMP on the prolactin gene are clearly mediated through distinct response pathways. |
Databáze: | OpenAIRE |
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