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SOCS2 negatively re...
SOCS2 negatively regulates growth hormone action in vitro and in vivo.
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Greenhalgh, Christopher J (author)
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Rico-Bautista, Elizabeth (author)
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- Lorentzon, Mattias, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine
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Thaus, Anne L (author)
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Morgan, Phillip O (author)
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Willson, Tracy A (author)
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Zervoudakis, Panagiota (author)
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Metcalf, Donald (author)
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Street, Ian (author)
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Nicola, Nicos A (author)
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Nash, Andrew D (author)
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Fabri, Louis J (author)
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Norstedt, Gunnar (author)
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine
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Flores-Morales, Amilcar (author)
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Alexander, Warren S (author)
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Hilton, Douglas J (author)
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(creator_code:org_t)
- 2005
- 2005
- English.
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In: The Journal of clinical investigation. - 0021-9738. ; 115:2, s. 397-406
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Abstract
Subject headings
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- Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30-50% increase in mature body size. Here we show that the SOCS2-/- phenotype is dependent upon the presence of endogenous growth hormone (GH) and that treatment with exogenous GH induced excessive growth in mice lacking both endogenous GH and SOCS2. This was reflected in terms of overall body weight, body and bone lengths, and the weight of internal organs and tissues. A heightened response to GH was also measured by examining GH-responsive genes expressed in the liver after exogenous GH administration. To further understand the link between SOCS2 and the GH-signaling cascade, we investigated the nature of these interactions using structure/function and biochemical interaction studies. Analysis of the 3 structural motifs of the SOCS2 molecule revealed that each plays a crucial role in SOCS2 function, with the conserved SOCS-box motif being essential for all inhibitory function. SOCS2 was found to bind 2 phosphorylated tyrosines on the GH receptor, and mutational analysis of these amino acids showed that both were essential for SOCS2 function. Together, the data provide clear evidence that SOCS2 is a negative regulator of GH signaling.
Keyword
- Amino Acid Motifs
- genetics
- Animals
- Body Weight
- drug effects
- genetics
- physiology
- DNA-Binding Proteins
- genetics
- metabolism
- Gene Expression Regulation
- genetics
- physiology
- Growth Hormone
- administration & dosage
- genetics
- physiology
- Insulin-Like Growth Factor I
- physiology
- Liver
- metabolism
- pathology
- Mice
- Mice
- Knockout
- Phosphorylation
- Protein Binding
- genetics
- physiology
- Receptors
- Somatotropin
- genetics
- metabolism
- Repressor Proteins
- genetics
- metabolism
- Signal Transduction
- drug effects
- genetics
- physiology
- Suppressor of Cytokine Signaling Proteins
- Trans-Activators
- genetics
- metabolism
- Tyrosine
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Greenhalgh, Chri ...
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Rico-Bautista, E ...
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Lorentzon, Matti ...
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Thaus, Anne L
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Morgan, Phillip ...
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Willson, Tracy A
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show more...
-
Zervoudakis, Pan ...
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Metcalf, Donald
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Street, Ian
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Nicola, Nicos A
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Nash, Andrew D
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Fabri, Louis J
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Norstedt, Gunnar
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Ohlsson, Claes, ...
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Flores-Morales, ...
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Alexander, Warre ...
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Hilton, Douglas ...
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show less...
- Articles in the publication
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The Journal of c ...
- By the university
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University of Gothenburg