Nutritional control of nucleocytoplasmic localization of cAMP-dependent protein kinase catalytic and regulatory subunits in Saccharomyces cerevisiae

In budding yeast, cAMP-dependent protein kinase (PKA) plays a central role in the nutritional control of metabolism, cell cycle, and transcription. Th is study shows that both the regulatory subunit Bcy1p and the catalytic sub unit Tpk1p associated with it are predominantly localized in the nucleus of rapidly growing cells. Activation of nuclear PKA by cAMP leads to fast ent ry of a significant part of Tpk1p into the cytoplasm, while the regulatory subunit remains nuclear, In contrast to rapidly proliferating cells, both B cy1p and Tpk1p are distributed over nucleus and cytoplasm in cells growing on a nonfermentable carbon source or in stationary phase cells. These resul ts demonstrate that at least two different mechanisms determine the subcell ular localization of PKA; cAMP controls the localization of Tpk1p, and the carbon source determines that of Bcy1p, The N-terminal domain of Bcy1p serv es to target it properly during logarithmic and stationary phase. Studies w ith Bcy1p mutant versions unable to concentrate in the nucleus revealed tha t cells producing them are less viable in stationary phase than wild type c ells, display delayed reproliferation following transfer to fresh growth me dium, and, as diploids, exhibit reduced efficiency of sporulation.