The molecular biology of interleukin 6 and its receptor.
Functional pleiotropy and redundancy are characteristic features of cytokines. Interleukin 6 (IL-6) is a typical example: IL-6 induces cellular differentiation or expression of tissue-specific genes; it is involved in processes such as antibody production in B cells, acute-phase protein synthesis in hepatocytes, megakaryocyte maturation, cytotoxic T cell differentiation, and neural differentiation of PC12 (pheochromocytoma) cells. It promotes growth of myeloma/plasmacytoma cells, T cells, keratinocytes and renal mesangial cells, and it inhibits growth of myeloid leukaemic cell lines and certain carcinoma cell lines. The IL-6 receptor consists of two polypeptide chains, a ligand-binding chain (IL-6R) and a non-ligand-binding, signal-transducing chain (gp130). Interaction of IL-6 with IL-6R triggers the association of gp130 and IL-6R, and the signal can be transduced through gp130. Association of gp130 with IL-6R is involved in the formation of high affinity binding sites. This two-chain model has been shown to be applicable to receptor systems for several other cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, IL-5 and nerve growth factor (NGF). The pleiotropy and redundancy of cytokines may be explained on the basis of this unique receptor system.
Kishimoto
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T
Department of Medicine III, Osaka University Medical School, Japan.
Hibi
M
M
Murakami
M
M
Narazaki
M
M
Saito
M
M
Taga
T
T
D000818:Animals; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry / Q000502:physiology*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction / Q000502:physiology
D006023:Glycoproteins; D015850:Interleukin-6; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6