Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling. / Greenhalgh, Christopher J; Metcalf, Donald; Thaus, Anne L; Corbin, Jason E; Uren, Rachel; Morgan, Phillip O; Fabri, Louis J; Zhang, Jian-Guo; Martin, Helene M; Willson, Tracy A; Billestrup, Nils; Nicola, Nicos A; Baca, Manuel; Alexander, Warren S; Hilton, Douglas J.
I: The Journal of Biological Chemistry, Bind 277, Nr. 43, 25.10.2002, s. 40181-4.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling
AU - Greenhalgh, Christopher J
AU - Metcalf, Donald
AU - Thaus, Anne L
AU - Corbin, Jason E
AU - Uren, Rachel
AU - Morgan, Phillip O
AU - Fabri, Louis J
AU - Zhang, Jian-Guo
AU - Martin, Helene M
AU - Willson, Tracy A
AU - Billestrup, Nils
AU - Nicola, Nicos A
AU - Baca, Manuel
AU - Alexander, Warren S
AU - Hilton, Douglas J
PY - 2002/10/25
Y1 - 2002/10/25
N2 - 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.
AB - 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.
KW - Animals
KW - DNA-Binding Proteins
KW - Growth Hormone
KW - Mice
KW - Mice, Transgenic
KW - Protein Binding
KW - Proteins
KW - Receptors, Somatotropin
KW - Recombinant Proteins
KW - Repressor Proteins
KW - Signal Transduction
KW - Suppressor of Cytokine Signaling Proteins
KW - Trans-Activators
U2 - 10.1074/jbc.C200450200
DO - 10.1074/jbc.C200450200
M3 - Journal article
C2 - 12208853
VL - 277
SP - 40181
EP - 40184
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 43
ER -
ID: 132900007