Cytokine signaling in the brain: putting a SOCS in it?
A new family of cytokine-inducible proteins, termed "suppressors of cytokine signaling" (SOCS), was discovered recently; these proteins function as negative regulators of signaling pathways involved in the cellular actions of many cytokines, growth factors, and hormones. Gene manipulation studies in mice point to the central importance of individual SOCS proteins in maintaining homeostasis by limiting cellular responses to specific cytokines or growth factors in a variety of different physiological systems. Cytokines modulate a wide variety of biological responses in the CNS, so members of the SOCS family might play crucial roles in regulating intracellular signaling by these effectors in both normal and disease states. Although to date studies of the neurobiology of the SOCS family have been limited, we know that many SOCS genes are constitutively expressed in the developing and adult brain, whereas the expression of others, particularly the SOCS1 and SOCS3 genes, can be highly regulated. Furthermore, roles for the SOCS are now evident in the modulation of neuroimmunoendocrine functions affected by a variety of cytokines, including leptin and members of the growth hormone and the interleukin-6/gp130 superfamilies. Overall, these findings point to the SOCS as likely crucial negative modulators in the temporal and spatial regulation and intensity of cytokine signaling and therefore actions in the CNS.
Wang
Jianping
J
The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Campbell
Iain L
IL
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D015213:Neuroimmunomodulation / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; 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