An Antibody Reactive with Domain 4 of the Platelet-derived Growth Factor β Receptor Allows BB Binding while Inhibiting Proliferation by Impairing Receptor Dimerization
作者： Theodore Shulman , Frederic G. Sauer , Robin M. Jackman , Chung Nan Chang , Nicholas F. Landolfi
关键词: Molecular biology 、 Biology 、 Monoclonal antibody 、 Receptor 、 Antibody 、 Platelet-derived growth factor receptor 、 Signal transduction 、 Platelet-derived growth factor 、 Growth factor 、 Extracellular
摘要: Abstract A panel of murine monoclonal antibodies was generated against the extracellular domain human platelet-derived growth factor (PDGF) β receptor (PDGFRβ). These were assayed for both ability to inhibit binding PDGF BB PDGFRβ+ cells as well capacity BB-mediated mitogenesis. As expected, all that could prevent also inhibited However one antibody (M4TS.11), with no detectable binding, a potent inhibitor proliferation induced by BB. Further characterization indicated M4TS.11 impaired PDGFRβ dimerization, revealing mechanism which it prevented Using deletion mutants portion PDGFRβ, determinant recognized this localized fourth indicating domain, is not involved in ligand actively participates dimerization and signal transduction. The responsive from baboon rabbit, limited humans making possible use evaluate therapeutic benefit interfering animal models disease.
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