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Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling.

Suppressor of cytokine signaling (SOCS)-2 is a member of a family of intracellular proteins implicated in the negative regulation of cytokine signaling. The generation of SOCS-2-deficient mice, which grow to one and a half times the size of their wild-type littermates, suggests that SOCS-2 may attenuate growth hormone (GH) signaling. In vitro studies indicate that, while SOCS-2 can inhibit GH action at low concentrations, at higher concentrations it may potentiate signaling. To determine whether a similar enhancement of signaling is observed in vivo or alternatively whether increased SOCS-2 levels repress growth in vivo, we generated and analyzed transgenic mice that overexpress SOCS-2 from a human ubiquitin C promoter. These mice are not growth-deficient and are, in fact, significantly larger than wild-type mice. The overexpressed SOCS-2 was found to bind to endogenous GH receptors in a number of mouse organs, while phosphopeptide binding studies with recombinant SOCS-2 defined phosphorylated tyrosine 595 on the GH receptor as the site of interaction. Together, the data implicate SOCS-2 as having dual effects on GH signaling in vivo.

Pubmed ID: 12208853

Authors

  • Greenhalgh CJ
  • Metcalf D
  • Thaus AL
  • Corbin JE
  • Uren R
  • Morgan PO
  • Fabri LJ
  • Zhang JG
  • Martin HM
  • Willson TA
  • Billestrup N
  • Nicola NA
  • Baca M
  • Alexander WS
  • Hilton DJ

Journal

The Journal of biological chemistry

Publication Data

October 25, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 22556

Mesh Terms

  • Animals
  • DNA-Binding Proteins
  • Growth Hormone
  • Mice
  • Mice, Transgenic
  • Protein Binding
  • Proteins
  • Receptors, Somatotropin
  • Recombinant Proteins
  • Repressor Proteins
  • Signal Transduction
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators