How do pleiotropic kinase hubs mediate specific signaling by TNFR superfamily members?
Tumor necrosis factor receptor (TNFR) superfamily members mediate the cellular response to a wide variety of biological inputs. The responses range from cell death, survival, differentiation, proliferation, to the regulation of immunity. All these physiological responses are regulated by a limited number of highly pleiotropic kinases. The fact that the same signaling molecules are involved in transducing signals from TNFR superfamily members that regulate different and even opposing processes raises the question of how their specificity is determined. Regulatory strategies that can contribute to signaling specificity include scaffolding to control kinase specificity, combinatorial use of several signal transducers, and temporal control of signaling. In this review, we discuss these strategies in the context of TNFR superfamily member signaling.
Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0375, USA. bschroefelbauer@ucsd.edu
Bärbel
B
Schröfelbauer
Alexander
A
Hoffmann
D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013379:Substrate Specificity; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D011494:Protein Kinases