Identification of a growth hormone-responsive STAT5-binding element in the rat insulin 1 gene
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Identification of a growth hormone-responsive STAT5-binding element in the rat insulin 1 gene. / Galsgaard, E D; Gouilleux, F; Groner, B; Serup, P; Billestrup, N; Nielsen, Jens Høiriis.
I: Molecular endocrinology (Baltimore, Md.), Bind 10, Nr. 6, 06.1996, s. 652-60.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of a growth hormone-responsive STAT5-binding element in the rat insulin 1 gene
AU - Galsgaard, E D
AU - Gouilleux, F
AU - Groner, B
AU - Serup, P
AU - Billestrup, N
AU - Nielsen, Jens Høiriis
PY - 1996/6
Y1 - 1996/6
N2 - GH and PRL stimulate both proliferation and insulin production in pancreatic beta-cells as well as in the rat insulinoma cell line RIN-5AH, We report here that human GH increases insulin mRNA levels in RIN-5AH cells via both somatogenic and lactogenic receptors. GH stimulated the rat insulin 1 promoter activity 2-fold, and this stimulation was abolished by introduction of a block mutation in a gamma-interferon-activated sequence (GAS)-like element (GLE) with the sequence 5'-TTCTGGGAA-3' located in the rat insulin 1 enhancer at position -330 to -322. This element, termed Ins-GLE, was able to confer GH responsiveness to a heterologous promoter. GH induced the binding of two protein complexes to the Ins-GLE. An antibody directed against the transcription factor STAT5 (signal transducer and activator of transcription) supershifted the GH-induced complexes. Furthermore, in COS7 cells transiently transfected with STAT5 and GH receptor cDNAs, it was found that expression of STAT5 was necessary for GH induction of these two DNA-binding complexes. These results suggest that GH stimulates insulin 1 promoter activity by inducing the binding of STAT5 to Ins-GLE.
AB - GH and PRL stimulate both proliferation and insulin production in pancreatic beta-cells as well as in the rat insulinoma cell line RIN-5AH, We report here that human GH increases insulin mRNA levels in RIN-5AH cells via both somatogenic and lactogenic receptors. GH stimulated the rat insulin 1 promoter activity 2-fold, and this stimulation was abolished by introduction of a block mutation in a gamma-interferon-activated sequence (GAS)-like element (GLE) with the sequence 5'-TTCTGGGAA-3' located in the rat insulin 1 enhancer at position -330 to -322. This element, termed Ins-GLE, was able to confer GH responsiveness to a heterologous promoter. GH induced the binding of two protein complexes to the Ins-GLE. An antibody directed against the transcription factor STAT5 (signal transducer and activator of transcription) supershifted the GH-induced complexes. Furthermore, in COS7 cells transiently transfected with STAT5 and GH receptor cDNAs, it was found that expression of STAT5 was necessary for GH induction of these two DNA-binding complexes. These results suggest that GH stimulates insulin 1 promoter activity by inducing the binding of STAT5 to Ins-GLE.
KW - Animals
KW - Binding Sites
KW - DNA-Binding Proteins
KW - Gene Expression Regulation, Neoplastic
KW - Growth Hormone
KW - Insulin
KW - Insulinoma
KW - Milk Proteins
KW - Promoter Regions, Genetic
KW - Proteins
KW - RNA, Messenger
KW - Rats
KW - STAT5 Transcription Factor
KW - Trans-Activators
KW - Tumor Cells, Cultured
KW - Up-Regulation
M3 - Journal article
C2 - 8776725
VL - 10
SP - 652
EP - 660
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 6
ER -
ID: 47972994