Protein Kinase A: A Master Kinase of Granulosa Cell Differentiation
| Autor: | Uma R. Chandran, Lynda Little-Ihrig, Mary Hunzicker-Dunn, Anthony J. Zeleznik, Pawan Puri, Nathan C. Law |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system Cellular differentiation CREB p38 Mitogen-Activated Protein Kinases Article Glycogen Synthase Kinase 3 03 medical and health sciences 0302 clinical medicine Animals Humans Protein kinase A Protein kinase B Cells Cultured beta Catenin Granulosa cell differentiation Granulosa Cells Multidisciplinary biology Kinase Ovary Cell Differentiation Rats Inbred Strains Cyclic AMP-Dependent Protein Kinases Molecular biology Rats 030104 developmental biology Gene Expression Regulation Mitogen-activated protein kinase Mutation biology.protein Female Follicle Stimulating Hormone Human Steroids Signal transduction hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep28132 |
| Popis: | Activation of protein kinase A (PKA) by follicle stimulating hormone (FSH) transduces the signal that drives differentiation of ovarian granulosa cells (GCs). An unresolved question is whether PKA is sufficient to initiate the complex program of GC responses to FSH. We compared signaling pathways and gene expression profiles of GCs stimulated with FSH or expressing PKA-CQR, a constitutively active mutant of PKA. Both FSH and PKA-CQR stimulated the phosphorylation of proteins known to be involved in GC differentiation including CREB, ß-catenin, AKT, p42/44 MAPK, GAB2, GSK-3ß, FOXO1, and YAP. In contrast, FSH stimulated the phosphorylation of p38 MAP kinase but PKA-CQR did not. Microarray analysis revealed that 85% of transcripts that were up-regulated by FSH were increased to a comparable extent by PKA-CQR and of the transcripts that were down-regulated by FSH, 76% were also down-regulated by PKA-CQR. Transcripts regulated similarly by FSH and PKA-CQR are involved in steroidogenesis and differentiation, while transcripts more robustly up-regulated by PKA-CQR are involved in ovulation. Thus, PKA, under the conditions of our experimental approach appears to function as a master upstream kinase that is sufficient to initiate the complex pattern of intracellular signaling pathway and gene expression profiles that accompany GC differentiation. |
| Databáze: | OpenAIRE |
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