Cutting edge: SOCS-1 is a potent inhibitor of IL-4 signal transduction.
IL-4 is an important regulator of the activation, proliferation, and differentiation of many hematopoetic cells. Many of these biological effects result from the activation of Janus kinases (JAK)1 and JAK3 and the transcription factor Stat6. Recent data suggest that members of the SOCS (suppressor of cytokine signaling) family of proteins can inhibit JAK-STAT signaling. We have examined the ability of SOCS family members to suppress IL-4 signaling, and we have found that SOCS-1 potently inhibits the activation of JAK1 kinase and Stat6 in response to IL-4. Furthermore, SOCS-1 can inhibit the induction of CD23 expression by IL-4. SOCS-2 does not inhibit induction of signaling by IL-4, while inhibition of IL-4 signaling by SOCS-3 can be detected in transient transfection systems, but not in stable cell lines. These studies implicate SOCS-1 in modulation of IL-4 signaling and suggest that SOCS-1 may play a role in regulating the immune response.
Losman
J A
JA
Integrated Program in Molecular, Cellular, and Biophysical Studies, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York 10032, USA.
Chen
X P
XP
Hilton
D
D
Rothman
P
P
D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D014162:Transfection
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3