Cyclic Amp-Independent Phosphoregulation Of Protein Kinase A In The Fission Yeast, Schizosaccharomyces Pombe

In the fission yeast, Schizosaccharomyces pombe, cyclic AMP (cAMP) and cAMP-dependent protein kinase (PKA) are not essential for cell viability under normal culturing conditions, making this organism attractive for investigating cAMP-independent mechanisms of PKA regulation. Here we show that S. pombe adenylate cyclase (cyr1Δ) mutants express significantly higher levels of the PKA catalytic subunit, Pka1, than wild type S. pombe cells, while expressing similar levels of the PKA regulatory subunit, Cgs1. Furthermore, in cyr1Δ cells, but not wild type cells, a substantial proportion of Pka1 protein is hyperphosphorylated by a mechanism dependent on the PKA regulatory subunit, Cgs1. Hyperphosphorylation of Pka1 is further induced in cyr1Δ cells, and to varying degrees in wild type S. pombe cells, in response to KCl stress, glucose derepression, and stationary phase growth. Our findings demonstrate the existence of a cAMP-independent mechanism(s) of PKA phosphoregulation in S. pombe, which we speculate may function to maintain certain PKA functions in conditions in which cAMP-dependent activities are downregulated.