A Direct Interaction between the N Terminus of Adenylyl Cyclase AC8 and the Catalytic Subunit of Protein Phosphatase 2A

Although protein scaffolding complexes compartmentalize pro-tein kinase A (PKA) and phosphodiesterases to optimize cAMP signaling, adenylyl cyclases, the sources of cAMP, have been implicated in very few direct protein interactions. The N termini of adenylyl cyclases are highly divergent, which hints at iso-form-specific interactions. Indeed, the Ca2-sensitive adenylyl cyclase 8 (AC8) contains a Ca2/calmodulin binding site on the N terminus that is essential for stimulation of activity by the capacitative entry of Ca2 in the intact cell. Here, we have used the N terminus of AC8 as a bait in a yeast two-hybrid screen of a human embryonic kidney (HEK) 293 cell cDNA library and identified the catalytic subunit of the serine/threonine protein phosphatase 2A (PP2AC) as a binding partner. Confirming the highly specific nature of this novel interaction, glutathione-S