PMP1(+), A SUPPRESSOR OF CALCINEURIN DEFICIENCY, ENCODES A NOVEL MAP KINASE PHOSPHATASE IN FISSION YEAST

Calcineurin is a highly conserved and ubiquitously expressed Ca2+- and calmodulin-dependent protein phosphatase. The in vivo role of calcine urin, however, is not fully understood. Here, we show that disruption of the calcineurin gene (ppb1(+)) in fission yeast results in a drasti c chloride ion (Cl-)-sensitive growth defect and that a high copy numb er of a novel gene pmp1(+) suppresses this defect, pmp1(+) encodes a p hosphatase, most closely related to mitogen-activated protein (MAP) ki nase phosphatases of the CL100/MKP-1 family, Pmp1 and calcineurin shar e an essential function in Cl- homeostasis, cytokinesis and cell viabi lity Pmp1 phosphatase dephosphorylates Pmk1, the third MAP kinase in f ission yeast, in vitro and in vivo, and is bound to Pmk1 in vivo, stro ngly suggesting that Pmp1 negatively regulates Pmk1 MAP kinase by dire ct dephosphorylation. Consistently, the deletion of pmk1+ suppresses t he Cl--sensitive growth defect of ppb1 null. Thus, calcineurin and the Pmk1 MAP kinase pathway may play antagonistic functional roles in the Cl- homeostasis.