Regulation of the MAP kinase pathway in Y1 adrenal cells

grantor: University of TorontoThe growth promoting effect of ACTH on adrenal cells 'in vivo ' is well established. Paradoxically, the effect of the hormone on cultured adrenal cells is growth inhibitory. Growth inhibition in adrenal cells is mediated by cAMP and PKA as demonstrated in studies with a PKA defective mutant adrenal cell line. Recent studies investigating the growth effects of ACTH have suggested that the hormone does promote cell mitogenesis, in cultured adrenal cells when it is administered in a short pulse. The increase in mitogenesis correlated with an increase in the phosphorylation and activity of the mitogen activated protein kinases, ERK 1 and ERK 2. These kinases are important regulators of cell proliferation, differentiation and development in a variety of cellular systems. In this thesis, I examined the pathway through which ERK 1/2 activities were increased in response to ACTH stimulation. My studies were carried out using the mouse adrenocortical tumor cell line, Y1, as an experimental system. (Abstract shortened by UMI.)M.Sc