Keyse S M
ICRF Molecular Pharmacology, Ninewells Hospital, Dundee, Scotland, UK.
Semin Cell Dev Biol. 1998 Apr;9(2):143-52. doi: 10.1006/scdb.1997.0219.
A family of dual specificity (Thr/Tyr) MAP kinase phosphatases (MKPs) have been identified in mammalian cells. These enzymes are implicated in negative feedback control of MAP kinase activity. This idea is supported by genetic and biochemical evidence which implicates homologous enzymes in the regulation of MAP kinases in yeasts and Drosophila. However, recent work in yeasts has shown that, in addition to these dual specificity MKPs, 'classical' tyrosine-specific phosphatases are also involved in the regulated dephosphorylation of MAP kinases. A picture is emerging in which a complex interplay between upstream activators and multiple protein phosphatases is responsible for the regulation of MAP kinase activity. The activities, substrate specificities and subcellular localisation of these protein phosphatases are likely to be key determinants of the biological outcome of signalling through different MAP kinase pathways in mammalian cells and tissues.
在哺乳动物细胞中已鉴定出一个双特异性（苏氨酸/酪氨酸）丝裂原活化蛋白激酶磷酸酶（MKP）家族。这些酶参与丝裂原活化蛋白激酶活性的负反馈控制。这一观点得到了遗传和生化证据的支持，这些证据表明酵母和果蝇中调节丝裂原活化蛋白激酶的同源酶也参与其中。然而，最近在酵母中的研究表明，除了这些双特异性MKP外，“经典”酪氨酸特异性磷酸酶也参与丝裂原活化蛋白激酶的调节性去磷酸化。一幅图景正在浮现，其中上游激活剂和多种蛋白磷酸酶之间的复杂相互作用负责丝裂原活化蛋白激酶活性的调节。这些蛋白磷酸酶的活性、底物特异性和亚细胞定位可能是哺乳动物细胞和组织中通过不同丝裂原活化蛋白激酶途径进行信号传导的生物学结果的关键决定因素。
