Martín Humberto, Flández Marta, Nombela César, Molina María
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense, 28040-Madrid, Spain.
Mol Microbiol. 2005 Oct;58(1):6-16. doi: 10.1111/j.1365-2958.2005.04822.x.
Because of their key role in cell signalling, a rigorous regulation of mitogen-activated protein kinases (MAPKs) is essential in eukaryotic physiology. Whereas the use of binding motifs and scaffold proteins guarantees the selective activation of a specific MAPK pathway, activating kinases and downregulating phosphatases control the appropriate intensity and timing of MAPK activation. Tyrosine, serine/threonine and dual-specificity phosphatases co-ordinately dephosphorylate and thereby inactivate MAPKs. In budding yeast, enzymes that belong to these three types of phosphatases have been shown to counteract the MAPKs that govern the cellular response to varied extracellular stimuli. Studies carried out with these yeast phosphatases have expanded our knowledge of essential key aspects of the biology of these negative regulators, such as their function, the mechanisms that operate in their modulation by MAPK pathways and their binding to MAPK substrates. Furthermore, yeast MAPK phosphatases have been shown to play additional and essential roles in MAPK-mediated signalling, controlling MAPK localization or cross-talk among pathways. This review stresses the importance of these negative regulators in eukaryotic signalling by discussing the recent developments and perspectives in the study of yeast MAPK phosphatases.
由于丝裂原活化蛋白激酶（MAPKs）在细胞信号传导中发挥关键作用，因此在真核生物生理学中对其进行严格调控至关重要。虽然结合基序和支架蛋白的使用确保了特定MAPK途径的选择性激活，但激活激酶和下调磷酸酶则控制着MAPK激活的适当强度和时机。酪氨酸、丝氨酸/苏氨酸和双特异性磷酸酶协同作用使MAPKs去磷酸化，从而使其失活。在芽殖酵母中，已证明属于这三种磷酸酶类型的酶可对抗控制细胞对各种细胞外刺激反应的MAPKs。对这些酵母磷酸酶进行的研究扩展了我们对这些负调控因子生物学重要关键方面的认识，例如它们的功能、由MAPK途径调控它们的机制以及它们与MAPK底物的结合。此外，酵母MAPK磷酸酶已被证明在MAPK介导的信号传导中发挥额外的重要作用，控制MAPK的定位或途径间的相互作用。本综述通过讨论酵母MAPK磷酸酶研究的最新进展和前景，强调了这些负调控因子在真核生物信号传导中的重要性。
