Mitogens such as growth factors, depend on the nature of target cell, can induce cell migration, differentiation, apoptosis or survival, as well as stimulation or inhibition of cell proliferation. The regulation of growth factor signaling pathway is tightly regulated in both time and space, however corruption along this pathway can lead to the course of oncogenic transformation and tumorigenesis. Remarkable progress has been made in understanding steps in regulation of mitogen-induced cellular reactions. Nonetheless, there is still a gap in our knowledge concerning the intracellular mechanisms which regulation cellular responses toward mitogenic stimuli. Effort has been made to define the steps of intracellular kinase cascades used for cells to transfer mitogenic signal from the cell surface to the nucleus. Central to such kinase cascades are the group of serine/threonine kinases comprising the MAP kinase family. Here we propose to study the role of one group of MAP kinase, the BMK1 group, because the BMK1 pathway has been implicated in mitogens induced immediate early genes. The major focus here is to analyze the structure/function of the components in the activating module of BMK1 pathway and to characterize the regulatory mechanism and biological role of BMK1 pathway in heregulin-induced breast cancer cells activation. To do this we will utilize a combination of biochemical, immunologic and molecular biologic approaches. Implicit in the proposed studies is the development of new approaches to intervene in cancer-related diseases.
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