IGE BINDING PROTEIN--A MULTIFUNCTIONAL ANIMAL LECTIN

IGE结合蛋白--一种多功能动物凝集素

• 批准号: 2061370
• 负责人: FU-TONG LIU
• 金额: $ 20.09万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2061370
• 关键词: analytical ultracentrifugation; antibody receptor; binding proteins; chemical binding; chemical structure function; gel filtration chromatography; glycoproteins; immunoglobulin E; laboratory mouse; laboratory rabbit; laboratory rat; lectin; mast cell

The focus of this project is on IgE-binding protein (epsilon-BP) with emphasis on its modulatory role on mast cell functions. Epsilon-BP is a 31,000 Mr protein identified in rat basophilic leukemia (RBL) cells and is now known as soluble lectin designated with different names by other laboratories and appears to have multiple functions. The protein has wide tissue distribution, is found on the cell surface and also secreted under certain conditions. Epsilon-BP has specificity for distinct oligosaccharide structures that have a terminal galactose not masked by sialic acids and it functions at least bivalently. In addition to binding IgE, epsilon-BP binds to surfaces of various cell types, including mast cells. First, the molecular basis for multivalency of epsilon-BP will be elucidated. We have evidence that epsilon-BP has a tendency to self-associate through intermolecular interactions involving the amino-- terminal domain, resulting in dimers or oligomers. This property of epsilon-BP will be further investigated, including equilibrium ultracentrifugation analysis and binding to lactosyl-Sepharose 4B containing varying densities of lactose. Another explanation for bivalency of epsilon-BP is the formation of a dimer through an inter-molecular disulfide linkage. The molecular mechanism for the covalent dimerization of epsilon-BP will be investigated. Second, cell surface glycoprotein ligands for epsilon-BP will be identified. Preliminary studies indicate that epsilon-BP is attached to glycoconjugates on the surface of mast cells and only a small number of different glycoproteins species on RBL cell surface are recognized by epsilon-BP. Significantly, one of these glycoproteins is the high affinity IgE receptor (Fc-epsilon-RI). We will focus on isolation and characterization of another epsilon-BP-reactive Mr 150,00 glycoprotein. We will then investigate possible variation in epsilon-BP recognition of FC-epsilon-RI on mast cells at various differentiation stages or activation status. Third, the function of epsilon-BP as a multifunctional modulator molecule will be established. Having demonstrated epsilon-BP's multivalent property and recognition of cell surface glycoproteins, especially Fc-epsilon-RI, we propose that this lectin has the potential to modulate cellular functions of mast cells mediated by these glycoproteins. We have already shown that epsilon-BP potentiates Fc-epsilon-RI-mediated mast cell activation. We will further substantiate this modulator role of epsilon-BP and investigate the mechanism for the observed potentiating effect.

本项目的重点是研究与之相关的ige结合蛋白（epsilon-BP）