JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling

Blood. 2001 Jan 1;97(1):221-6. doi: 10.1182/blood.v97.1.221.


JAB/suppressor of cytokine signaling 1 (SOCS1) STAT-induced STAT inhibitor-1 (SSI-1) (JAB/SOCS1/SSI-1) is an SH2-domain-containing protein that is induced by and negatively regulates signaling by a number of cytokines including interleukin-4 (IL-4), IL-6, interferon (IFN)-gamma, prolactin, growth hormone, and erythropoietin. The role of JAB/SOCS1/SSI-1 in IL-2 signaling has been analyzed. JAB/SOCS1/SSI-1 is strongly induced by IL-2 in peripheral blood T cells, and JAB/SOCS1/SSI-1 overexpression strongly inhibits IL-2-induced signal transducer and activator of transcription-5 (Stat5) phosphorylation and transcriptional activity. In cotransfection experiments, JAB/SOCS1/SSI-1 associates with both Jak1 and Jak3; however, JAB/SOCS1/SSI-1 had a greater effect on Jak1 tyrosine phosphorylation and kinase activity. JAB/SOCS1/SSI-1 also interacts with IL-2Rbeta, and this interaction requires the A region (residues 313-382) of IL-2Rbeta. However, this interaction was not essential for the inhibitory action of JAB. Thus, JAB/SOCS1/SSI-1 is an IL-2-induced inhibitor of IL-2 signaling that functions by inhibiting Jak kinase activity. This suggests an important role for JAB/SOCS1/SSI-1 in regulating T-cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology*
  • Carrier Proteins / physiology
  • Cell Line
  • DNA-Binding Proteins / antagonists & inhibitors
  • Enzyme Activation / drug effects
  • Gene Expression / drug effects
  • Humans
  • Interleukin-2 / physiology*
  • Intracellular Signaling Peptides and Proteins*
  • Janus Kinase 1
  • Milk Proteins*
  • Phosphorylation / drug effects
  • Precipitin Tests
  • Protein-Tyrosine Kinases / drug effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / pharmacology
  • Repressor Proteins / physiology
  • STAT5 Transcription Factor
  • Signal Transduction / drug effects*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology
  • Trans-Activators / antagonists & inhibitors
  • Transcription, Genetic / drug effects
  • Transfection


  • Carrier Proteins
  • DNA-Binding Proteins
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Milk Proteins
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Repressor Proteins
  • SOCS1 protein, human
  • STAT5 Transcription Factor
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Janus Kinase 1