Graduate School of Medical Sciences
A partnership with the Sloan Kettering Institute

Jochen Buck

Niroshana Anandasabapathy



The second messenger molecule cAMP, which modulates cell growth and differentiation in organisms from bacteria to higher eukaryotes, is produced by adenylyl cyclases. Mammals possess two distinct classes of adenylyl cyclase, the hormone-responsive, transmembrane adenylyl cyclases (tmAC) and the bicarbonate-regulated Soluble Adenylyl Cyclase (sAC). sAC, which we purified and cloned in collaboration with Dr. Lonny Levin's Laboratory, and tmACs define distinct cAMP signaling pathways within eukaryotic cells. tmACs are modulated by heterotrimeric G proteins in response to extracellular signals acting through seven-transmembrane spanning, G protein-coupled receptors. In contrast, sAC is directly regulated by bicarbonate ions suggesting it functions as the physiological carbon dioxide chemosensor. sAC most closely resembles cyanobacterial adenylyl cyclases, and regulation by bicarbonate ions is also conserved in these cyclases from blue...

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