Shiozaki K, Russell P
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Nature. 1995 Dec 14;378(6558):739-43. doi: 10.1038/378739a0.
In fission yeast the onset of mitosis is brought about by Cdc2/Cdc13 kinase, which is inhibited by the Wee1/Mik1 tyrosine kinases and activated by Cdc25 tyrosine phosphatase. This control network integrates many signals, including those that monitor DNA replication, DNA damage and cell size. We report here that a fission yeast MAP kinase pathway links the cell-cycle G2/M control with changes in the extracellular environment that affect cell physiology. Fission yeast spc1- mutants have a G2 delay that is greatly exacerbated by growth in high osmolarity media and nutrient limitation. A lethal interaction of spc1 and cdc25 mutations shows that Spc1 promotes the onset of mitosis. Spc1 is a MAP kinase homologue that is activated by Wis1 kinase in response to osmotic stress and nutrient limitation. Spc1 is inactivated by Pyp1, a phosphatase previously identified as a mitotic inhibitor. Pyp1 dephosphorylates only tyrosine-173 of Spc1, unlike the dual-specificity phosphatases that have been shown to regulate other MAP kinases.
在裂殖酵母中，有丝分裂的开始是由Cdc2/Cdc13激酶引发的，该激酶受到Wee1/Mik1酪氨酸激酶的抑制，并被Cdc25酪氨酸磷酸酶激活。这个调控网络整合了许多信号，包括那些监测DNA复制、DNA损伤和细胞大小的信号。我们在此报告，裂殖酵母的一条促分裂原活化蛋白激酶（MAP激酶）信号通路将细胞周期G2/M调控与影响细胞生理的细胞外环境变化联系起来。裂殖酵母spc1-突变体存在G2期延迟，在高渗培养基中生长和营养限制时这种延迟会大大加剧。spc1和cdc25突变之间的致死性相互作用表明，Spc1促进有丝分裂的开始。Spc1是一种MAP激酶同源物，在渗透胁迫和营养限制时被Wis1激酶激活。Spc1被Pyp1失活，Pyp1是一种先前被鉴定为有丝分裂抑制剂的磷酸酶。与已证明可调节其他MAP激酶的双特异性磷酸酶不同，Pyp1仅使Spc1的酪氨酸-173去磷酸化。
