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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Christopher J Greenhalgh
  • Donald Metcalf
  • Anne L Thaus
  • Jason E Corbin
  • Rachel Uren
  • Phillip O Morgan
  • Louis J Fabri
  • Jian-Guo Zhang
  • Helene M Martin
  • Tracy A Willson
  • Billestrup, Nils
  • Nicos A Nicola
  • Manuel Baca
  • Warren S Alexander
  • Douglas J Hilton

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.

TidsskriftThe Journal of Biological Chemistry
Udgave nummer43
Sider (fra-til)40181-4
Antal sider4
StatusUdgivet - 25 okt. 2002

ID: 132900007