Román Elvira, Alonso-Monge Rebeca, Gong Qianghong, Li Dongmei, Calderone Richard, Pla Jesús
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
FEMS Yeast Res. 2009 Sep;9(6):942-55. doi: 10.1111/j.1567-1364.2009.00545.x. Epub 2009 Jun 26.
Mitogen activated protein kinase (MAPK) cascades are signal transduction mechanisms present in eukaryotic cells that allow adaptation to environmental changes. MAPK activity is mainly regulated by dual phosphorylation in a TXY motif present in the kinase subdomain VIII as well as dephosphorylation by specific phosphatases. The Cek1 MAPK is involved in filamentous growth in Candida albicans and is an important determinant of virulence in this microorganism; its activation is controlled by the Sho1 adaptor protein. Here we show that Cek1 phosphorylation is regulated by quorum sensing (QS). Cek1 phosphorylation is prevented by farnesol, a compound that also regulates the dimorphic transition in this fungus. Farnesol also induced the activation of Mkc1, the MAPK of the cell integrity pathway. The role of farnesol in Cek1 phosphorylation is independent of the Chk1 histidine kinase, a putative QS sensor, as revealed by genetic analysis. In addition, Cek1, not Hog1, is degraded by proteasome, as revealed by the use of a conditional lethal protein degradation mutant. Our data therefore describe two different mechanisms (QS and protein degradation) that control a MAPK pathway that regulates virulence in a fungal pathogen.
丝裂原活化蛋白激酶（MAPK）级联反应是真核细胞中存在的信号转导机制，可使细胞适应环境变化。MAPK活性主要通过激酶亚结构域VIII中TXY基序的双重磷酸化以及特定磷酸酶的去磷酸化来调节。Cek1 MAPK参与白色念珠菌的丝状生长，是该微生物毒力的重要决定因素；其激活受Sho1衔接蛋白控制。在此我们表明，Cek1磷酸化受群体感应（QS）调节。法尼醇可阻止Cek1磷酸化，法尼醇也是一种调节该真菌二态转变的化合物。法尼醇还诱导了细胞完整性途径的MAPK即Mkc1的激活。基因分析表明，法尼醇在Cek1磷酸化中的作用独立于推定的QS传感器Chk1组氨酸激酶。此外，使用条件致死性蛋白质降解突变体发现，被蛋白酶体降解的是Cek1而非Hog1。因此，我们的数据描述了控制调节真菌病原体毒力的MAPK途径的两种不同机制（QS和蛋白质降解）。
