STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver

Mol Cell Endocrinol. 1999 Dec 20;158(1-2):111-6. doi: 10.1016/s0303-7207(99)00175-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Cattle
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / metabolism*
  • Female
  • Growth Hormone / pharmacology*
  • Immediate-Early Proteins / metabolism
  • Injections, Intraperitoneal
  • Liver / metabolism
  • Mammary Glands, Animal / metabolism
  • Mice
  • Milk Proteins*
  • Organ Specificity
  • Proteins / metabolism*
  • Repressor Proteins*
  • STAT5 Transcription Factor
  • Signal Transduction / physiology*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators / deficiency
  • Trans-Activators / metabolism*
  • Transcription Factors*

Substances

  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Milk Proteins
  • Proteins
  • Repressor Proteins
  • STAT5 Transcription Factor
  • Socs2 protein, mouse
  • Socs3 protein, mouse
  • Stat5a protein, mouse
  • Stat5b protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators
  • Transcription Factors
  • cytokine inducible SH2-containing protein
  • Growth Hormone