LIGAND INDUCED EVENTS IN LYMPHOCYTES

细胞表面膜是细胞内部和外部的界面 环境。膜上的受体接收和处理传入信号 在细胞内发出信号并启动复杂的反应。鲜为人知 淋巴细胞膜上的受体如何调节它们的功能。在……里面 这个提议我主要对发生的细胞事件感兴趣 在淋巴细胞与配体结合后，更具体地说，要遵循命运 和不同类别淋巴细胞受体的跨膜连接 分子在交联化后到细胞骨架元件，以及到 研究该系统可能通过磷酸化来调节。 受体或与受体相互作用并使它们相互关联的蛋白质 参数与生理事件。 我已经证明，配基结合可以将一些受体从洗涤剂转化为 易溶于洗涤剂不溶状态。对于表面免疫球蛋白来说 转化与有丝分裂信号的传递有关。这 转化是服从于生化实验的，这将允许 受体不解性与可能的配体诱导的相关性研究 洗涤剂中受体及相关蛋白的磷酸化 不溶的基质。这种磷酸化反应可能在 信号传递或受体调节。来自这些的数据 实验将与生理事件相关。 因此，我的具体目标包括：优先事项1.确定 洗涤剂不溶物质的固定化和诱导机理 大鼠淋巴细胞膜蛋白的形态。优先事项2.配体诱导 与受体相互作用的受体或蛋白质的磷酸化 磷酸化反应的可能调节作用将是 下定决心。优先事项3.膜蛋白与 细胞骨架元素将在有丝分裂原激活的细胞上进行检测。一个 细胞活化与特异性受体的相关性 将进行蛋白质-细胞骨架蛋白质的相互作用。优先事项4.、 这些实验的长期目标是开发针对 淋巴细胞基质中与膜相互作用的新元素 蛋白质。

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.