Neurochemical signal transduction and the control of tissue specific gene expression are investigated, using the pineal gland as a model. The details of the chemical and ionic components of transmembrane signalling processing and of neural and tissue specific regulation of gene expression are analyzed. Signal transduction in this system is of special interest because cAMP and cGMP are regulated by dual receptor mechanisms which appear to interact at the level of regulation of adenylyl and guanylyl cyclases. One leg of these pathways activates these enzymes via GTP binding regulatory proteins, similar to GSalpha. Current activities are focused on the role of MEKA in signal transduction. MEKA is a 33 kDa substrate of protein kinase A and exists as a cytoplasmic complex with GS/beta/gamma. Immunoprecipitation is being used to isolate and study the phosphorylation states of GSalpha, adenylyl cyclase and guanylyl cyclase complexes. In the area of the neural and developmental control of gene expression, advances have been made in purifying N-acetyltransferase and hydroxyindole-O-methyltransferase, and in isolating cDNA clones coding for these enzymes. A human hydroxyindole-O-methyltransferase cDNA clone has been sequenced and the gene has been located on the pseudoautosomal region of the sex chromosomes. The major hormonal product of the pineal gland is melatonin and this project has extended its interest in signal transduction to the question of how melatonin acts on the pituitary gland.
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