Sugiura R, Toda T, Shuntoh H, Yanagida M, Kuno T
Department of Pharmacology, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
EMBO J. 1998 Jan 2;17(1):140-8. doi: 10.1093/emboj/17.1.140.
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.
钙调神经磷酸酶是一种高度保守且广泛表达的Ca2+和钙调蛋白依赖性蛋白磷酸酶。然而，钙调神经磷酸酶在体内的作用尚未完全明确。在此，我们发现裂殖酵母中钙调神经磷酸酶基因（ppb1(+)）的破坏会导致严重的氯离子（Cl-）敏感型生长缺陷，并且一个新基因pmp1(+)的高拷贝数可抑制该缺陷。pmp1(+)编码一种磷酸酶，与CL100/MKP-1家族的丝裂原活化蛋白（MAP）激酶磷酸酶关系最为密切。Pmp1和钙调神经磷酸酶在Cl-稳态、胞质分裂和细胞活力方面具有重要功能。Pmp1磷酸酶在体外和体内均可使裂殖酵母中的第三种MAP激酶Pmk1去磷酸化，且在体内与Pmk1结合，这强烈表明Pmp1通过直接去磷酸化对Pmk1 MAP激酶进行负调控。同样，pmk1(+)的缺失可抑制ppb1缺失菌株对Cl-敏感的生长缺陷。因此，钙调神经磷酸酶和Pmk1 MAP激酶途径可能在Cl-稳态中发挥拮抗性功能作用。
