Negative regulation of cytokine signaling by CIS/SOCS family proteins and their roles in inflammatory diseases.
Immune and inflammatory systems are controlled by multiple cytokines, including interleukins (ILs) and interferons. These cytokines exert their biological functions through Janus tyrosine kinases (JAKs) and STAT transcription factors. The CIS (cytokine-inducible SH2 protein) and SOCS (suppressors of cytokine signaling) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine responses, including those that regulate the inflammatory systems. In this review, we focused on the molecular mechanism of the action of CIS/SOCS family proteins and their roles in inflammatory diseases. Furthermore, we illustrate several approaches for treating inflammatory diseases by modulating extracellular and intracellular signaling pathways.
Hanada
T
T
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Maidashi, 812-8582 Higashi-ku, Fukuoka, Japan.
Kinjyo
I
I
Inagaki-Ohara
K
K
Yoshimura
A
A
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000502:physiology*; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000502:physiology; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000502:physiology
D002352:Carrier Proteins; D016207:Cytokines; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051193:Toll-Like Receptors; D014157:Transcription Factors; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse