Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-I in vivo

Am J Physiol Gastrointest Liver Physiol. 2006 Sep;291(3):G472-81. doi: 10.1152/ajpgi.00218.2005. Epub 2006 Mar 30.


Suppressors of cytokine signaling (SOCS) typically limit cytokine receptor signaling via the JAK-STAT pathway. Considerable evidence demonstrates that SOCS2 limits growth hormone (GH) action on body and organ growth. Biochemical evidence that SOCS2 binds to the IGF-I receptor (IGF-IR) supports the novel possibility that SOCS2 limits IGF-I action. The current study tested the hypothesis that SOCS2 normally limits basal or IGF-I-induced intestinal growth and limits IGF-IR signaling in intestinal epithelial cells. Intestinal growth was assessed in mice homozygous for SOCS2 gene deletion (SOCS2 null) and wild-type (WT) littermates at different ages and in response to infused IGF-I or vehicle or EGF and vehicle. The effects of SOCS2 on IGF-IR signaling were examined in ex vivo cultures of SOCS2 null and WT intestine and Caco-2 cells. Compared with WT, SOCS2 null mice showed significantly enhanced small intestine and colon growth, mucosal mass, and crypt cell proliferation and decreases in radiation-induced crypt apoptosis in jejunum. SOCS2 null mice showed significantly greater growth responses to IGF-I in small intestine and colon. IGF-I-stimulated activation of IGF-IR and downstream signaling intermediates were enhanced in the intestine of SOCS2 null mice and were decreased by SOCS2 overexpression in Caco-2 cells. SOCS2 bound directly to the endogenous IGF-IR in Caco-2 cells. The intestine of SOCS2 null mice also showed enhanced growth responses to infused EGF. We conclude that SOCS2 normally limits basal and IGF-I- and EGF-induced intestinal growth in vivo and has novel inhibitory effects on the IGF-IR tyrosine kinase pathway in intestinal epithelial cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / drug effects
  • Aging / physiology*
  • Animals
  • Cell Line
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Insulin-Like Growth Factor I / administration & dosage*
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / physiology*
  • Intestines / cytology*
  • Intestines / drug effects
  • Intestines / growth & development*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*


  • Socs2 protein, mouse
  • Suppressor of Cytokine Signaling Proteins
  • Insulin-Like Growth Factor I