LIGAND INDUCED EVENTS IN LYMPHOCYTES

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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.