JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling.
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.
Sporri
B
B
Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Kovanen
P E
PE
Sasaki
A
A
Yoshimura
A
A
Leonard
W J
WJ
D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D008894:Milk Proteins; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1