A fundamental problem in developmental biology concerns the mechanisms by which cells interact in a harmonious fashion such that their spatial and temporal organization results in a functional metazoan. One such mechanism involves the use of diffusible substances, released by one cell (or tissue) which affect the behavior of a specific target cell (or tissue). A well documented, but poorly understood example is that of chemotactic signalling, a seemingly ubiquitous phenomenon in embryogenesis and development. The long term objective of this research is to understand the biogenesis of a chemotactic signalling system. The model system is D. discoideum, for which pulses of cAMP function as the chemotactic signal. Production of the chemotactic signal, once initiated, is autocatalytic. The primary focus of this research is the role of the cAMP cell surface receptor in regulating the production of cAMP pulses. Current lines of investigation consist of biochemical analysis of receptor phosphorylation, and the characterization of CAR-kinase, the enzyme which specifically phosphorylates the ligand-occupied form of the cAMP receptor in plasma membranes. The results of this research will provide new information concerning a novel enzyme (kinase) that phosphorylates the cell membrane receptor for the chemoattractant molecule, cyclic AMP, and about the role of receptor phosphorylation in signal transduction. Of particular interest is how such phenomena are regulated to produce sustained oscillations of cAMP such that pulses of cAMP are produced.
