The tale of soluble receptors and binding proteins: from bench to bedside.
Our approach of isolating proteins from a rich source of human proteins by ligand-affinity-chromatography enabled rapid and efficient isolation of not only soluble receptors corresponding to cell-associated receptors, but also independent binding-proteins and associated enzymes. No other approach would yield the latter. During the early 80's we prepared the tools and the infrastructure that enabled the subsequent 20 years of achievements. Thus we described eight soluble receptors (R) and binding proteins (BP) for various cytokines including the IL-6R, IFN-gammaR, TNFRI, TNFRII, LDLR, IFN-alpha/betaR, IL-18BP and IL-32BP identified as Proteinase 3. The isolation of the soluble IFN-alpha/beta receptor led to the cloning of its long sought cell surface ligand binding counterpart. We have established the concept that soluble receptors and binding proteins are normal constituents of body fluids in healthy individuals and that the levels of these biomarkers are modulated in various pathological situations. Each of these proteins contributed to basic science, one of them serves as a basis for therapy and some others are in various stages of clinical development.
Novick
Daniela
D
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. daniela.novick@weizmann.ac.il
Rubinstein
Menachem
M
D000818:Animals; D002846:Chromatography, Affinity; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000302:isolation & purification*; D018121:Receptors, Cytokine / Q000302:isolation & purification*; D011973:Receptors, LDL / Q000302:isolation & purification*
D036341:Intercellular Signaling Peptides and Proteins; D018121:Receptors, Cytokine; D011973:Receptors, LDL; C118370:interleukin-18 binding protein