The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells
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The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells. / Rønn, Sif G; Hansen, Johnny A; Lindberg, Karen; Karlsen, Allan E; Billestrup, Nils.
I: Molecular endocrinology (Baltimore, Md.), Bind 16, Nr. 9, 09.2002, s. 2124-34.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells
AU - Rønn, Sif G
AU - Hansen, Johnny A
AU - Lindberg, Karen
AU - Karlsen, Allan E
AU - Billestrup, Nils
PY - 2002/9
Y1 - 2002/9
N2 - 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.
AB - 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.
KW - Cell Division
KW - Cells, Cultured
KW - DNA-Binding Proteins
KW - Electrophoretic Mobility Shift Assay
KW - Flow Cytometry
KW - Growth Hormone
KW - Humans
KW - Insulin
KW - Islets of Langerhans
KW - Milk Proteins
KW - Proteins
KW - RNA, Messenger
KW - Repressor Proteins
KW - STAT3 Transcription Factor
KW - STAT5 Transcription Factor
KW - Signal Transduction
KW - Suppressor of Cytokine Signaling Proteins
KW - Trans-Activators
KW - Transcription Factors
U2 - 10.1210/me.2002-0082
DO - 10.1210/me.2002-0082
M3 - Journal article
C2 - 12198248
VL - 16
SP - 2124
EP - 2134
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 9
ER -
ID: 132900056