We have used Dictyostelium and mammalian adipocytes as parallel systems to study the regulation of differentiation by extracellular signalling. Dictyostelium responds to secreted, extracellular cAMP which regulates development through receptor/G-protein signalling systems. We have fully characterized the cAMP receptor family with respect to gene organization, protein structure and spatial and temporal expression. Binding specificities for each receptor have been described and suggest that appropriate cAMP analogs will only activate a single cAMP receptor and its linked effector systems. DNA elements required for expression of each receptor have also been identified. These analyses permit a detailed study of receptor regulation and function through promoter fusion studies and expression of chimeric receptors in receptor null cells. 3T3-Ll cells will differentiate into adipocytes after exposure to dexamethasone. This hormone will also inhibit the synthesis of the lymphokine in these cells. We have shown that addition of IL-6 to 3T3-Ll cells treated with dexamethasone inhibits differentiation and the expression of adipocyte-specific gene expression. Other studies on adipocyte-specific gene expression are in progress. Perilipin is a protein associated with periphery of lipid droplets in adipocytes. We have isolated cDNAs for perilipin and deduced its amino acid sequence. We have shown that perilipin is expressed specifically in adipocytes and showed that its developmental regulation is associated with the appearance of lipid droplets but other adipocyte-specific genes have been used to study gene expression during differentiation of 3T3-Ll adipoblasts and in primary cultures of isolated adipocytes.
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