The growth and differentiation of eukaryotic cells is often modulated by extracellular molecules. Receptors on cell surfaces are stimulated by these signal which can then activate a series of effectors which produce a variety of intracellular second messengers such as cAMP, IP, DAG, calcium and cGMP. Each of these is capable of activating specific protein kinases. Ultimately, the proteins phosphorylated by these kinases are suggested to interact with cellar components to modulate the expression of the eukaryotic genome and promote cell proliferation and cytodifferentiation. We have been studying these processes in Dictyostelium discoideum, an organism whose developmental cycle is controlled by extracellular cAMP. We have established a linkage of the expression of individual gene families with the accumulation of specific intracellular second messengers. Additionally, we have isolated genes encoding components of the signal transduction system. Two genes have been characterized which code for cell- surface cAMP receptor molecules. Data indicate that these receptors traverse the plasma membrane seven times as other receptors which interact with G-proteins. Two genes encode different sized mRNAs which are expressed at different times during the developmental cycle. One is induced during early development; the second is detected during cytodifferentiation. We have also been studying genes for GTP-binding proteins. Two novel genes have been isolated which also exhibit differences in their regulation during development. One is expressed in growing cells and is repressed during development; the other is only expressed in multicellular aggregates.
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