Metabolic Release of Cell Surface Proteins

The proliferation and differentiation of 1)maphoid cells can be stimulated bv specific antigens, antigen-antibody complexes, plant mitogens and hormones. The initial event in the response to these diverse agents is believed to be the binding of stimulator molecules to receptors located on the cell surface (1, 2). However, the mechanism by which the binding of receptor to its ligand triggers cell differentiation and division is unknown. Prerequisite to the understanding of the cellular events occurring subsequent to surface receptor-stimulator interactions is knowledge of the nature of such receptor molecules and the manner in which they are associated with the cell membrane. We have approached the problem of identification of cell surface receptors bv developing a method based on the lactoperoxidase-catalyzed radioiodination of proteins (3), which allows covalent labeling of proteins present on the surface of lymphoid cells (4). Electron microscopic evidence indicated that only the outer surface of the cell is labeled by this method. In addition, sufficient radioactivity is incorporated into the surface to allow fractionation of iodinated proteins by a variety of techniques. This method has facilitated the isolation of immunoglobulin from the surface of mouse spleen cells (5) and human and mouse thymus cells. I Since cell viability is not adversely affected by this gentle method of iodination, physiological studies of accessible surface proteins may be carried out using living lymphocytes. The experiments reported herein demonstrate that many proteins associated with the cell surface exist in a dynamic state. We