Lee B N, Elion E A
Department of Biological Chemistry, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12679-84. doi: 10.1073/pnas.96.22.12679.
In haploid Saccharomyces cerevisiae, the mating and invasive growth (IG) pathways use the same mitogen-activated protein kinase kinase kinase kinase (MAPKKKK, Ste20), MAPKKK (Ste11), MAPKK (Ste7), and transcription factor (Ste12) to promote either G(1) arrest and fusion or foraging in response to distinct stimuli. This exquisite specificity is the result of pathway-specific receptors, G proteins, scaffold protein, and MAPKs. It is currently not thought that the shared signaling components function under the basal conditions of vegetative growth. We tested this hypothesis by searching for mutations that cause lethality when the STE11 gene is deleted. Strikingly, we found that Ste11, together with Ste20, Ste7, Ste12, and the IG MAPK Kss1, functions in a third pathway that promotes vegetative growth and is essential in an och1 mutant that does not synthesize mannoproteins. We term this pathway the STE vegetative growth (SVG) pathway. The SVG pathway functions, in part, to promote cell wall integrity in parallel with the protein kinase C pathway. During vegetative growth, the SVG pathway is inhibited by the mating MAPK Fus3. By contrast, the SVG pathway is constitutively activated in an och1 mutant, suggesting that it senses intracellular changes arising from the loss of mannoproteins. We predict that general proliferative functions may also exist for other MAPK cascades thought only to perform specialized functions.
在单倍体酿酒酵母中,交配和侵袭性生长(IG)途径使用相同的丝裂原活化蛋白激酶激酶激酶激酶(MAPKKKK,Ste20)、MAPKKK(Ste11)、MAPKK(Ste7)和转录因子(Ste12)来促进G(1)期停滞和融合,或响应不同刺激进行觅食。这种精确的特异性是途径特异性受体、G蛋白、支架蛋白和MAPK的结果。目前认为共享的信号成分在营养生长的基础条件下不起作用。我们通过寻找在STE11基因缺失时导致致死性的突变来检验这一假设。令人惊讶的是,我们发现Ste11与Ste20、Ste7、Ste12和IG MAPK Kss1一起,在促进营养生长的第三条途径中发挥作用,并且在不合成甘露糖蛋白的och1突变体中是必不可少的。我们将这条途径称为STE营养生长(SVG)途径。SVG途径部分地与蛋白激酶C途径并行发挥作用,以促进细胞壁完整性。在营养生长期间,SVG途径受到交配MAPK Fus3的抑制。相比之下,SVG途径在och1突变体中组成性激活,表明它感知到由于甘露糖蛋白缺失而产生的细胞内变化。我们预测,其他仅被认为执行特殊功能的MAPK级联可能也存在一般增殖功能。