Shared cytokine signaling receptors: structural insights from the gp130 system.
The vast majority of cytokine signaling is mediated by "shared" receptors that form central signaling components of higher-order complexes incorporating ligand-specific receptors. These include the common gamma chain (gamma(c)), common beta chain (beta(c)), and gp130, as well as others. These receptors have the dual tasks of cross-reactive cytokine recognition, and formation of precisely oriented multimeric signaling assemblies. Currently, detailed structural information on a shared receptor complex exists only for gp130, which is a highly pleiotropic shared cytokine signaling receptor essential for mammalian cell growth and homeostasis. To date, more than 10 different four-helix bundle ligands have been identified that incorporate gp130, or one of its close relatives such as LIF receptor, into functional oligomeric signaling complexes. In this review we summarize our current knowledge of shared receptor recognition and activation, with a focus on gp130. We discuss recent structural and functional information to analyze overall architectural assemblies of gp130 cytokine complexes and probe the basis for the extreme cross-reactivity of gp130 for its multiple cytokine ligands.
Boulanger
Martin J
MJ
Department of Microbiology, Stanford University School of Medicine, Stanford, California 94305-5124, USA.
Garcia
K Christopher
KC
D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D019382:Human Growth Hormone / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D016207:Cytokines; C494199:IL6ST protein, human; D008024:Ligands; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D019382:Human Growth Hormone; D050822:Cytokine Receptor gp130