Fox D, Smulian A G
Department of Pathology; Infectious Disease Division, University of Cincinnati College of Medicine, 231 Bethesda Ave, Cincinnati, OH, USA.
Mol Microbiol. 1999 Nov;34(3):451-62. doi: 10.1046/j.1365-2958.1999.01606.x.
Signal transduction pathways are important in the adaptive response of microbes to their environment. A Pneumocystis carinii extracellular signal-regulated protein kinase (MAPK) homologue, Mkp1, has been isolated by sequence similarity screening of P. carinii genomic DNA. The Mkp1 of P. carinii shows closest homology to other fungal MAP kinases involved in cell integrity signal transduction cascades, including Slt2p/Mpk1p of Saccharomyces cerevisiae, Mkc1 of Candida albicans and Mps1 of Magnaporthe grisea. Defects of Slt2p in S. cerevisiae result in phenotypes of slow growth, and temperature sensitivity in the absence of an osmostabilizer. Overexpression of mkp1 in a strain with the slt2Delta defect fully restored the normal growth rate, and partially reduced lysis at elevated temperatures. Complementation of the slt2Delta defect by Mkp1 demonstrates that Mkp1 is a functional MAP kinase, and that it may be the MAP kinase component of a similar signal transduction cascade within P. carinii. Furthermore, Mkp1 is activated in vitro upon the exposure of P. carinii to conditions of oxidative stress. The investigation of a MAP kinase signal transduction pathway of P. carinii will result in both a better understanding of the mechanism the organism utilizes to respond to environmental changes, and a system to assay responses to these changes.
信号转导通路在微生物对其环境的适应性反应中很重要。通过对卡氏肺孢子虫基因组DNA进行序列相似性筛选，分离出了一种卡氏肺孢子虫细胞外信号调节蛋白激酶（MAPK）同源物Mkp1。卡氏肺孢子虫的Mkp1与参与细胞完整性信号转导级联反应的其他真菌MAP激酶显示出最密切的同源性，包括酿酒酵母的Slt2p/Mpk1p、白色念珠菌的Mkc1和稻瘟病菌的Mps1。酿酒酵母中Slt2p的缺陷会导致生长缓慢的表型，以及在没有渗透压稳定剂的情况下对温度敏感。在具有slt2Delta缺陷的菌株中过表达mkp1可完全恢复正常生长速率，并部分降低高温下的裂解。Mkp1对slt2Delta缺陷的互补作用表明Mkp1是一种功能性MAP激酶，并且它可能是卡氏肺孢子虫内类似信号转导级联反应的MAP激酶成分。此外，卡氏肺孢子虫暴露于氧化应激条件下时，Mkp1在体外被激活。对卡氏肺孢子虫MAP激酶信号转导通路的研究将有助于更好地理解该生物体用于应对环境变化的机制，以及建立一个检测对这些变化反应的系统。
