The progression of activated (G1-phase) T cells into S-phase, and ultimately, mitosis is initiated by the binding of the T cell- derived growth factor, interleukin 2 (IL2) to high affinity cell surface receptors. At present, the intracellular pathways involved in the propagation of mitogenic signals in IL2-stimulated T cells are unknown. Although the IL2 receptor does not contain an intrinsic protein tyrosine kinase (PTK) domain, IL2 receptor occupancy stimulates the phosphorylation of intracellular proteins at tyrosyl residues. The long-term goal of this project is to define the mechanism by which ligand-stimulated IL2 receptors initiate and propagate growth-regulatory signals from the plasma membrane to the nucleus. The present study will utilize homogeneous populations of IL2-responsive, murine and human T cells to address the following specific aims: (1) To further define the interactions of the ligand-bound IL2 receptor with various non- receptor PTKs normally expressed in T cells. (2) To characterize IL2 receptor signaling functions and growth factor sensitivities in a panel of T cell clones transfected with genes (p60c-src, polyomavirus middle T antigen) whose protein products alter PTK activity in these cells. These studies will provide novel insights into the interactions of receptors for hormone-like "cytokines" with non-receptor enzymes, PTKs, and into the role of protein tyrosine phosphorylation in signal transduction leading to proliferation of specific cells of the immune system.
