The proposed research will identify at the molecular level the pathways utilized by the PRL-R in regulating the growth of normal and malignant T lymphocytes. First, the structural-functional determinants of the transmembrane and intracytoplasmic domains of the PRL-R will be mapped through the transfection of chimeric receptors into T cell lines. These chimeric receptors will be composed of the extracellular domain of the granulocyte-macrophage colony stimulating factor receptor (GM-CSF-R) and deletional mutants of the intracellular domain of the PRL-R. The T-cell clones containing the chimeric receptors will then be used to study the contributions of the intracellular and transmembrane domains of the PRL-R to T lymphocyte proliferation and the nuclear translocation of PRL. Second, PRL-R binding proteins will be identified by coimmunop- recipitation studies, and their ability to bind to the mutant chimeric receptors will be examined.
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