The SOCS-1 story.
SOCS-1 is an intracellular protein able to block the differentiation of leukemic M1 cells inducible by interferon gamma (IFN-gamma) or regulators using the gp130 receptor. Its transient production is readily inducible by cytokine stimulation, and SOCS-1 appears to be a negative feedback molecule, modulating or suppressing receptor signaling activated by at least eight cytokines. Mice lacking SOCS-1 develop a lethal neonatal syndrome including liver damage, depletion of T and B lymphocytes, and granulocyte-macrophage infiltration of the liver, lungs, pancreas, heart, and skin. These and the associated hematologic abnormalities in SOCS-1-/- mice can all be mimicked by the neonatal injection of high doses of IFN-gamma. The lethal neonatal disease in SOCS-1-/- mice is preventable by injection of antibodies to IFN-gamma or by crossing SOCS-1-/- mice with IFN-gamma-/- mice, identifying IFN-gamma as being essential for the initiation of the neonatal disease and death. IFN-gamma appears not to be overproduced in SOCS-1-/- mice, and the lethal disease may arise from hyperresponsiveness of -/- cells to normal levels of IFN-gamma. SOCS-1-/- mice allowed to survive the neonatal period by cross-mating with IFN-gamma-/- mice may well ultimately develop other disease states, because loss of SOCS-1 potentially renders them hyperresponsive to other cytokine signaling.
Metcalf
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The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D006410:Hematopoiesis; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018909:src Homology Domains
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma