A mitogenic peptide has been identified on the surface of both cultured fibroblasts and mouse liver. The primary objectives of this research proposal are to establish the role of this endogenous growth-stimulatory peptide in normal cellular proliferation, and to purify the factor. Work will be initiated on purifying the factor via two separate approaches. The first utilizes standard biochemical techniques, whereas the second involves the generation of a monoclonal antibody against the mitogen. The two pathways are complementary; isolation of a monoclonal antibody will simplify the biochemical purification of the mitogen (through affinity chromatography), and the biochemical purification of the mitogen will increase the chances of success in obtaining a monoclonal antibody (by providing highly mitogen enriched fractions for immunization). Once a specific probe of the mitogen has been obtained it will be possible to study the role of this factor in cellular proliferation. It will be determined if the mitogenic activity is preferentially expressed during a certain part of the cell cycle; if the factor is preferentially expressed during a certain stage of growth; if treatment of quiescent cells with either synergistic growth factors, or growth-inhibitory peptides, alters the expression and/or release of the mitogenic factor from the membrane; and if certain transformed lines contain and/or secrete large quantities of this factor. This last point is of particular interest due to the recent findings that overproduction of endogenous growth regulatory proteins is associated with transformation, and that viral oncogenes have been linked to cellular growth promoting molecules. It will also be determined whether the factor is active while membrane bound, or if membrane release is required for activity. These studies should generate an understanding of the regulation and expression of this mitogen on the cell surface, and how this regulation is related to cell growth.
| Ratner, N; Hong, D M; Lieberman, M A et al. (1988) The neuronal cell-surface molecule mitogenic for Schwann cells is a heparin-binding protein. Proc Natl Acad Sci U S A 85:6992-6 |
| Nagasaki, T; Lieberman, M A (1987) Growth-stimulatory action of plasma membrane-associated growth factor. A synergistic effect with platelet-poor plasma. Exp Cell Res 170:170-4 |
| Nagasaki, T; Lieberman, M A (1987) Heparin potentiates the action of plasma membrane-associated growth stimulatory activity. J Cell Physiol 133:365-71 |
| Grupp, S A; Lieberman, M A; Harmony, J A (1985) Inhibition of lymphocyte proliferation by detergent-solubilized mouse liver membranes. J Cell Biol 101:380-5 |
