We are also doing detailed expression studies of naturally occurring, activating receptor mutants. We have identified the cysteine residues responsible for receptor dimerization, and we have begun to define the role of dimerization in receptor activation. Our goal is to understand how calcium binding to the receptor leads to receptor and G protein activation, and to identify sites on the receptor extracellular domain that could serve as targets for therapeutic intervention in disorders such as hyperparathyroidism. After the successful positional cloning of the gene, we are pursuing a wide-ranging series of studies to elucidate its structure and function. The sequence of this 610 amino acid protein, menin, shows no similarity to other known proteins and does not contain defined functional motifs.
Recent work shows, however, that menin is localized to the nucleus.
We expect that ongoing studies will provide insights into menin's function and provide an opportunity to test the consequences of the many different germline mutations that have already been identified in subjects with MEN1 and somatic mutations identified in sporadic endocrine tumors. Journal of Biological Chemistry, in press 2001. Identification and characterization of JunD Missense mutants that lack menin binding. Menin interacts with the AP1 transcription factor JunD and represses JunD activated transcription. Menin, the product of the MEN1 gene, is a nuclear protein.