Molecular mechanisms of cytokine receptor activation.
Cytokine receptors are transmembrane proteins that transmit a signal into the cell upon ligand binding. Commonly, these molecules have one hydrophobic segment of about 20-26 amino acids that is believed to span the membrane as a helix and this divides these receptors into extra- and intracellular components. By utilizing two different epitopes, the cytokines bridge two receptor chains, resulting in a close proximity of the intracellular component and thereby initiating the intracellular signalling cascade. The dimerization event is believed to be the mechanism by which the signal is transmitted across a membrane. In the light of new results obtained for the erythropoietin receptor, James A. Wells questioned whether any dimer would be sufficient. This review will expand upon the above question by discussing the more complex signal-transducing receptor subunits of the Interleukin-6 type family of cytokines. Based on the recently solved quaternary structure of the Insulin receptor, possible analogies will be confronted.
Grötzinger
Joachim
J
Department of Biochemistry, Christian-Albrechts-Universität zu Kiel, Germany. jgroetzinger@biochem.uni-kiel.de
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D050822:Cytokine Receptor gp130; D019281:Dimerization; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000737:chemistry; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000502:physiology*; D019947:Receptors, Interleukin-6 / Q000737:chemistry; D011986:Receptors, Somatotropin / Q000737:chemistry; D015398:Signal Transduction
D015703:Antigens, CD; D000939:Epitopes; C494199:IL6ST protein, human; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D011986:Receptors, Somatotropin; D050822:Cytokine Receptor gp130; D011972:Receptor, Insulin