Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans
Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans
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DOI：
10.1128/ec.3.1.14-26.2004
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发表时间：
2004-02-01
期刊：
影响因子：
--
通讯作者：
Heitman, J
中科院分区：
文献类型：
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作者：
Hicks, JK;D'Souza, CA;Heitman, J
我们早期的研究结果表明，环腺苷酸依赖性蛋白激酶的功能，在信号级联调节交配和毒力的新型隐球菌变种。Grubii（血清型A）。缺乏血清型A蛋白激酶A（PKA）催化亚基Pka 1的突变体不能交配，不能产生黑色素或荚膜，并且在动物模型中是无毒的，而缺乏PKA调节亚基Pkr 1的突变体过度产生荚膜并且是高毒力的。因为已经观察到其他突变在两种不同的C.本文对血清型为D的新形线虫（Grubii变种[血清型A]和新形线虫变种[血清型D]）的PKA基因进行了功能分析。令人惊讶的是，Pka 1催化亚基不需要交配，单倍体子实体，或黑色素或胶囊生产的血清型D菌株。在这里，我们确定了第二个PKA催化亚基基因，PY-42，这是目前在血清型A和D株的C。新人类不同的Pka 2催化亚基被发现调节交配，单倍体子实体，和毒力因子的生产血清型D菌株。相反，Pka 2在血清型A菌株中的交配、黑色素产生或荚膜形成中没有作用。我们的研究说明了在人类真菌病原体的相关但不同的变种或亚种的进化过程中，信号通路的不同组分是如何被增选和功能性专门化的。
Our earlier findings established that cyclic AMP-dependent protein kinase functions in a signaling cascade that regulates mating and virulence of Cryptococcus neoformans var. grubii (serotype A). Mutants lacking the serotype A protein kinase A (PKA) catalytic subunit Pka1 are unable to mate, fail to produce melanin or capsule, and are avirulent in animal models, whereas mutants lacking the PKA regulatory subunit Pkr1 overproduce capsule and are hypervirulent. Because other mutations have been observed to confer different phenotypes in two diverged varieties of C. neoformans (grubii variety [serotype A] and neoformans variety [serotype D]), we analyzed the functions of the PKA genes in the serotype D neoformans variety. Surprisingly, the Pka1 catalytic subunit was not required for mating, haploid fruiting, or melanin or capsule production of serotype D strains. Here we identify a second PKA catalytic subunit gene, PY-42, that is present in both serotype A and D strains of C. neoformans. The divergent Pka2 catalytic subunit was found to regulate mating, haploid fruiting, and virulence factor production in serotype D strains. In contrast, Pka2 has no role in mating, melanin production, or capsule formation in serotype A strains. Our studies illustrate how different components of signaling pathways can be co-opted and functionally specialized during the evolution of related but distinct varieties or subspecies of a human fungal pathogen.