STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver.
Suppressor of cytokine signalling (SOCS) proteins act as part of a classical negative feedback loop regulating cytokine signal transduction. Expression of SOCS proteins is induced in response to cytokines and down-regulates the cytokine signal by inhibiting the JAK/STAT pathway. Growth hormone (GH) was previously shown to induce strong transient expression of SOCS-3 and to a lesser extent CIS, SOCS-1 and SOCS-2 in mouse liver (Adams, T.E., Hansen, J.A., Starr, R., Nicola, N.A., Hilton, D.J., Billestrup, N., 1998. Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of cytokine receptor signalling. J. Biol. Chem. 273, 1285-1287.). In this work we have compared GH-induced SOCS gene expression in wild-type and STAT5b-deficient mice, and show that STAT5b is required for the induction of SOCS-2 and SOCS-3 in liver. In contrast, the absence of STAT5b has no effect on the GH-induced expression of CIS and SOCS-2 mRNA in the mammary gland. Suprisingly, there is no activation of SOCS-3 expression in mammary glands of wild-type and STAT5b mutant mice following GH administration. These results highlight both tissue- and factor-specific differences in the regulation of SOCS gene expression by STAT5a/b.
Davey
H W
HW
Dairy Science Group, AgResearch, Ruakura, Hamilton, New Zealand. daveyh@agresearch.cri.nz
McLachlan
M J
MJ
Wilkins
R J
RJ
Hilton
D J
DJ
Adams
T E
TE
D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008894:Milk Proteins; D009928:Organ Specificity; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000172:deficiency / Q000378:metabolism*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D013006:Growth Hormone; D017874:Immediate-Early Proteins; D008894:Milk Proteins; D011506:Proteins; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C491409:Socs2 protein, mouse; C491411:Socs3 protein, mouse; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse