LIGAND INDUCED EVENTS IN LYMPHOCYTES

淋巴细胞中配体诱导的事件

• 批准号: 3129507
• 负责人: BRUCE A WODA
• 金额: $ 9.79万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129507
• 关键词: affinity chromatography; antiserum; cell cell interaction; crosslink; cytoskeleton; densitometry; gel electrophoresis; immune complex; immunoglobulins; immunoprecipitation; leukocyte activation /transformation; membrane activity; monoclonal antibody; phosphorylation; physiology; polymerization; radiotracer; tissue /cell culture

Cell surace membranes are the interface between the internal and external environment. Receptors in the membrane receive and process incoming signals and initiate complex responses within the cell. Little is known about how receptors in lymphocyte membranes mediate their functions. In this proposal I am primarily interested in the cellular events which occur in lymphocytes after ligand binding, more specifically, to follow the fate and transmembrane linkage of different classes of lymphocyte receptor molecules to cytoskeletal elements after they are cross-linked, and to study the possible regulation of this system by phosphorylation of receptors or proteins which interact with receptors and to correlate these parameters with physiologic events. I have shown that ligand binding converts some receptors from a detergent soluble to a detergent insoluble state. For surface immunoglobulin this conversion is correlated with the transmission of a mitogenic signal. This conversion is amenable to biochemical experiments which will allow a correlated study of receptor insolubilization and possible ligand induced phosphorylation of receptors and associated proteins in the detergent insoluble matrix. Such phosphorylation reactions may be important in signal transmission or receptor regulation. The data from these experiments will be correlated with physiologic events. My specific aims include, therefore: Priority 1., The determination of the mechanism of the immobilization and induction of the detergent insoluble form of rat lymphocyte membrane proteins. Priority 2., The ligand induced phosphorylation of receptors or proteins which interact with receptors and the possible regulatory role of phosphorylation reactions will be determined. Priority 3., The association of membrane proteins with cytoskeletal elements will be examined on mitogen activated cells. A correlation between cell activation and specific receptor protein-cytoskeletal protein interactions will be made. Priority 4., The long term goal of these experiments is to develop antisera directed against novel elements of the lymphocyte matrix which interact with membrane proteins.

细胞表面膜是细胞内外的界面 环境 细胞膜上的受体接受并处理传入的信息 信号并在细胞内启动复杂的反应。 知之甚少 淋巴细胞膜上的受体如何调节它们的功能。 在 这个建议我主要感兴趣的细胞事件发生 在配体结合后的淋巴细胞中，更具体地说， 以及不同类型淋巴细胞受体的跨膜连接 分子与细胞骨架元件交联后， 研究这个系统的可能调控磷酸化的 受体或与受体相互作用的蛋白质， 生理事件的参数。 我已经证明配体结合可以将一些受体从去污剂 可溶于洗涤剂不溶状态。 对于表面免疫球蛋白， 转化与促有丝分裂信号的传递相关。 这 转换是服从生化实验，这将允许一个 受体不溶解和可能的配体诱导的相关研究 洗涤剂中受体和相关蛋白的磷酸化 不溶性基质 这样的磷酸化反应可能是重要的， 信号传递或受体调节。 这些数据 实验将与生理事件相关联。 因此，我的具体目标包括：的确定 洗涤剂不溶物的固定化和诱导机理 大鼠淋巴细胞膜蛋白的形式。 优先事项2，配体诱导 受体或与受体相互作用的蛋白质的磷酸化， 磷酸化反应可能的调节作用将是 测定 优先事项3，膜蛋白与 将在促分裂原活化的细胞上检查细胞骨架元件。 一 细胞活化与特异性受体的相关性 将产生蛋白质-细胞骨架蛋白质相互作用。 优先事项4.，的 这些实验的长期目标是开发针对 与膜相互作用的淋巴细胞基质的新成分 proteins.