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 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.
Sugiura
R
R
Department of Pharmacology, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
Toda
T
T
Shuntoh
H
H
Yanagida
M
M
Kuno
T
T
D000595:Amino Acid Sequence; D019703:Calcineurin / Q000172:deficiency / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1; D005656:Fungal Proteins; D016153:Genes, Suppressor; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D002712:Chlorides; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C102726:Pmk1 protein, Magnaporthe grisea; C110459:Pmp1 protein, S pombe; D019703:Calcineurin; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases