PROPERTIES OF A LYMPHOMA CELL TYROSINE PROTEIN KINASE: There is increasing evidence that tyrosine protein kinases have an important role in T lymphocyte activation and cell cycle progression. We have identified a tyrosine protein kinase of apparent molecular weight of 56,000 (pp56Tcell). This enzyme is specific to T lymphoctyes and undergoes phosphorylation by protein kinase C during T lymphocyte activation. The general goal of this application is to determine the function of pp56Tcell in T cell activation. We have developed highly sensitive immunoblotting techniques that allow us to measure the activation pp56Tcell and other tyrosine protein kinases as well as the activation of protein kinase C. These techniques allow us to study these kinases in T cells and determine if their activation correlates with physiological responses. Thus the role of these enzymes will be evaluated in the response of T cells to a wide variety of mitogenic agents. The regulation of pp56Tcell is complex and involves phosphorylation at several sites. These phosphorylation reactions will be studied in detail in order to understand their function and the mechanisms that underlie their regulation. The biosynthetic pathway of pp56Tcell will be characterized to determine if this is regulated by agents that alter the phosphorylation of pp56Tcell. The studies on pp56Tcell will be aided by the production of monoclonal antibodies to pp56Tcell. Antibodies to phosphotyrosine have permitted us to identify a large number of potential substrates for pp56Tcell. These substrates will be purified and characterized in order to determine the function of the tyrosine phosphorylation that we have observed in T cells. The results of this research may provide new insights into the biochemical events involved in the regulation of the activation and growth of normal and malignant cells of the T lymphocyte lineage.
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