The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation
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The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation. / Richter, H E; Albrektsen, T; Billestrup, Nils.
In: Journal of Molecular Endocrinology, Vol. 30, No. 2, 04.2003, p. 139-50.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation
AU - Richter, H E
AU - Albrektsen, T
AU - Billestrup, Nils
PY - 2003/4
Y1 - 2003/4
N2 - GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator of transcription (STAT)-5 signalling pathway. Within minutes of treatment, GH induced the tyrosine phosphorylation, nuclear localization and DNA binding of STAT5. Importantly, there was no evidence that STAT5 acted via an interaction with peroxisome proliferator-activated receptor gamma. To further understand the mechanism of STAT5 action, we reconstituted the inhibition of aP2 in a non-adipogenic cell line. Using this system, we showed that the ability of GH to inhibit a 520 bp aP2 reporter was largely dependent upon the presence of either STAT5A or STAT5B. Mutant analysis confirmed that the tyrosine phosphorylation of STAT5 was essential for this signalling. However, STAT5's C-terminal transactivation domain was fully dispensable for this inhibition. Taken together, these data confirm a key regulatory role of STAT5 in adipose tIssue and point to STAT5 as the repressing modulator of GH-mediated inhibition in primary preadipocytes.
AB - GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator of transcription (STAT)-5 signalling pathway. Within minutes of treatment, GH induced the tyrosine phosphorylation, nuclear localization and DNA binding of STAT5. Importantly, there was no evidence that STAT5 acted via an interaction with peroxisome proliferator-activated receptor gamma. To further understand the mechanism of STAT5 action, we reconstituted the inhibition of aP2 in a non-adipogenic cell line. Using this system, we showed that the ability of GH to inhibit a 520 bp aP2 reporter was largely dependent upon the presence of either STAT5A or STAT5B. Mutant analysis confirmed that the tyrosine phosphorylation of STAT5 was essential for this signalling. However, STAT5's C-terminal transactivation domain was fully dispensable for this inhibition. Taken together, these data confirm a key regulatory role of STAT5 in adipose tIssue and point to STAT5 as the repressing modulator of GH-mediated inhibition in primary preadipocytes.
KW - Adipocytes
KW - Animals
KW - Carrier Proteins
KW - Cell Differentiation
KW - Cells, Cultured
KW - DNA-Binding Proteins
KW - Fatty Acid-Binding Proteins
KW - Gene Expression Regulation
KW - Genes, Reporter
KW - Growth Hormone
KW - Humans
KW - Janus Kinase 2
KW - Milk Proteins
KW - Nuclear Proteins
KW - Phosphorylation
KW - Promoter Regions, Genetic
KW - Protein Isoforms
KW - Protein-Tyrosine Kinases
KW - Proto-Oncogene Proteins
KW - RNA, Messenger
KW - Rats
KW - Receptors, Cytoplasmic and Nuclear
KW - STAT5 Transcription Factor
KW - Signal Transduction
KW - Trans-Activators
KW - Transcription Factors
KW - Tumor Suppressor Proteins
KW - Tyrosine
M3 - Journal article
C2 - 12683938
VL - 30
SP - 139
EP - 150
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
SN - 0952-5041
IS - 2
ER -
ID: 132899964