Agarwal Charu, Schultz David J, Perlin Michael H
Department of Biology, Program on Disease Evolution, University of Louisville Louisville, KY, USA.
Front Microbiol. 2010 Nov 29;1:127. doi: 10.3389/fmicb.2010.00127. eCollection 2010.
The dependence of Protein Kinase A (PKA) activity on cAMP levels is an important facet of the dimorphic switch between budding and filamentous growth as well as for pathogenicity in some fungi. To better understand these processes in the pathogenic fungus Ustilago maydis, we characterized the structure and biochemical functions of two phosphodiesterase (PDE) genes. Phosphodiesterases are enzymes involved in cAMP turnover and thus, contribute to the regulation of the cAMP-PKA signaling pathway. Two predicted homologs of PDEs were identified in the genome of U. maydis and hypothesized to be involved in cAMP turnover, thus regulating activity of the PKA catalytic subunit. Both umpde1 and umpde2 genes contain domains associated with phosphodiesterase activity predicted by InterPro analysis. Biochemical characterization of recombinantly produced UmPde1 (U. maydis Phosphodiesterase I) and UmPde2 demonstrated that both enzymes have phosphodiesterase activity in vitro, yet neither was inhibited by the phosphodiesterase inhibitor IBMX. Moreover, UmPde1 is specific for cAMP, while UmPde2 has broader substrate specificity, utilizing cAMP and cGMP as substrates. In addition, UmPde2 was also found to have nucleotide phosphatase activity that was higher with GMP compared to AMP. These results demonstrate that UmPde1 is a bona fide phosphodiesterase, while UmPde2 has more general activity as a cyclic nucleotide phosphodiesterase and/or GMP/AMP phosphatase. Thus, UmPde1 and UmPde2 likely have important roles in cell morphology and development and share some characteristics with a variety of non-fungal phosphodiesterases.
蛋白激酶A(PKA)活性对环磷酸腺苷(cAMP)水平的依赖性,是芽殖与丝状生长之间的二态性转换以及某些真菌致病性的一个重要方面。为了更好地理解致病真菌玉米黑粉菌中的这些过程,我们对两个磷酸二酯酶(PDE)基因的结构和生化功能进行了表征。磷酸二酯酶是参与cAMP周转的酶,因此有助于调节cAMP-PKA信号通路。在玉米黑粉菌的基因组中鉴定出两个预测的PDE同源物,并推测它们参与cAMP周转,从而调节PKA催化亚基的活性。umpde1和umpde2基因均包含通过InterPro分析预测的与磷酸二酯酶活性相关的结构域。重组产生的玉米黑粉菌磷酸二酯酶I(UmPde1)和UmPde2的生化表征表明,这两种酶在体外均具有磷酸二酯酶活性,但均未被磷酸二酯酶抑制剂异丁基甲基黄嘌呤(IBMX)抑制。此外,UmPde1对cAMP具有特异性,而UmPde2具有更广泛的底物特异性,可利用cAMP和环磷酸鸟苷(cGMP)作为底物。此外,还发现UmPde2具有核苷酸磷酸酶活性,与AMP相比,其对GMP的活性更高。这些结果表明,UmPde1是一种真正的磷酸二酯酶,而UmPde2作为一种环核苷酸磷酸二酯酶和/或GMP/AMP磷酸酶具有更广泛的活性。因此,UmPde1和UmPde2可能在细胞形态和发育中发挥重要作用,并与多种非真菌磷酸二酯酶具有一些共同特征。