pmp1 + , a suppressor of calcineurin deficiency, encodes a novel MAP kinase phosphatase in fission yeast

Calcineurin is a highly conserved and ubiquitously expressed Ca 2+ ‐ and calmodulin‐dependent protein phosphatase. The in vivo role of calcineurin, however, is not fully understood. Here, we show that disruption of the calcineurin gene ( ppb1 + ) in fission yeast results in a drastic chloride ion (Cl − )‐sensitive growth defect and that a high copy number of a novel gene pmp1 + suppresses this defect. pmp1 + encodes a phosphatase, most closely related to mitogen‐activated protein (MAP) kinase phosphatases of the CL100/MKP‐1 family. Pmp1 and calcineurin share an essential function in Cl − homeostasis, cytokinesis and cell viability. Pmp1 phosphatase dephosphorylates Pmk1, the third MAP kinase in fission yeast, in vitro and in vivo , and is bound to Pmk1 in vivo , strongly suggesting that Pmp1 negatively regulates Pmk1 MAP kinase by direct dephosphorylation. Consistently, the deletion of pmk1 + suppresses the Cl − ‐sensitive growth defect of ppb1 null. Thus, calcineurin and the Pmk1 MAP kinase pathway may play antagonistic functional roles in the Cl − homeostasis.