The Buck and Levin lab focus on the second messenger molecule cAMP, which modulates cell growth and differentiation in organisms from bacteria to higher eukaryotes. cAMP is produced by adenylyl cyclases, and mammals possess two distinct classes of adenylyl cyclase, the hormone-responsive, transmembrane adenylyl cyclases (tmAC) and the bicarbonate-regulated Soluble Adenylyl Cyclase (sAC). The Levin-Buck laboratory purified and cloned sAC, and sAC is now studied in the combined “LevBuck” laboratory.
In eukaryotic cells, second messengers, such as cAMP, play multiple, disparate roles within in a single cell. This is achieved by compartmentalization into independently regulated signaling microdomains distributed throughout the cell. sAC is localized to multiple intracellular sites containing cAMP effectors where it provides the second messenger for intracellular cAMP signaling microdomains.
Distinct from transmembrane adenylyl cyclases, sAC is regulated by bicarbonate anions, and because bicarbonate exists inside cells in a nearly instantaneous equilibrium with carbon dioxide and pH, sAC and its evolutionarily related orthologs, which are found throughout the kingdoms of life, serve as Nature’s carbon dioxide/bicarbonate/pH sensors.
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