The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells
Research output: Contribution to journal › Journal article › Research › peer-review
GH is an important regulator of cell growth and metabolism. In the pancreas, GH stimulates mitogenesis as well as insulin production in beta-cells. The cellular effects of GH are exerted mainly through activation of the Janus kinase-signal transducer and activator of transcription (STAT) pathway. Recently it has been found that suppressors of cytokine signaling (SOCS) proteins are able to inhibit GH-induced signal transduction. In the present study, the role of SOCS-3 in GH signaling was investigated in the pancreatic beta-cell lines RIN-5AH and INS-1 by means of inducible expression systems. Via stable transfection of the beta-cell lines with plasmids expressing SOCS-3 under the control of an inducible promoter, a time- and dose-dependent expression of SOCS-3 in the cells was obtained. EMSA showed that SOCS-3 is able to inhibit GH-induced DNA binding of both STAT3 and STAT5 in RIN-5AH cells. Furthermore, using Northern blot analysis it was shown that SOCS-3 can completely inhibit GH-induced insulin production in these cells. Finally, 5-bromodeoxyuridine incorporation followed by fluorescence-activated cell sorting analysis showed that SOCS-3 inhibits GH-induced proliferation of INS-1 cells. These findings support the hypothesis that SOCS-3 is a major regulator of GH signaling in insulin-producing cells.
Original language | English |
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Journal | Molecular endocrinology (Baltimore, Md.) |
Volume | 16 |
Issue number | 9 |
Pages (from-to) | 2124-34 |
Number of pages | 11 |
ISSN | 0888-8809 |
DOIs | |
Publication status | Published - Sep 2002 |
- Cell Division, Cells, Cultured, DNA-Binding Proteins, Electrophoretic Mobility Shift Assay, Flow Cytometry, Growth Hormone, Humans, Insulin, Islets of Langerhans, Milk Proteins, Proteins, RNA, Messenger, Repressor Proteins, STAT3 Transcription Factor, STAT5 Transcription Factor, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Trans-Activators, Transcription Factors
Research areas
ID: 132900056