GENETIC INVESTIGATION OF CAMP-DEPENDENT PROTEIN-KINASE FUNCTION IN DROSOPHILA DEVELOPMENT
GENETIC INVESTIGATION OF CAMP-DEPENDENT PROTEIN-KINASE FUNCTION IN DROSOPHILA DEVELOPMENT
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DOI：
10.1101/gad.7.7a.1229
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发表时间：
1993-07-01
影响因子：
10.5
通讯作者：
KALDERON, D
中科院分区：
文献类型：
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作者：
LANE, ME;KALDERON, D
在真核生物中，cAMP依赖性蛋白激酶（PKA）已被证明介导对细胞内第二信使cAMP的绝大多数细胞反应。为了研究cAMP信号转导在果蝇发育中的作用，我们分离了果蝇PKA基因DC0中不同严重程度的突变，并对其进行了分子表征。生化测定表明，DC0是果蝇中唯一或主要的PKA催化亚基基因。一个强的和一个弱的DC0等位基因杂合的成年女性不能产卵，并显示出一个惊人的和新的缺陷，卵子发生，包括形成卵室含有多核护士细胞。两个弱DC 0等位基因杂合子的雌性是可育的，但产生的后代在胚胎发生中表现出各种缺陷，包括前胚盘阻滞和表皮图案的改变。动物合子无效DC0死亡的形态正常的第一龄幼虫，这意味着母亲编码的蛋白质，持续至少12小时，足以胚胎发生。弱DC0等位基因的半合子动物作为幼虫存活数天，但生长缓慢。在成人眼中的有丝分裂重组实验表明，DC0基因是不需要自主细胞活力或正常生长率。这些结果表明，cAMP介导的信号转导是必不可少的，在多细胞动物的发展过程中的各个阶段。
The cAMP-dependent protein kinase (PKA) has been shown to mediate the vast majority of cellular responses to the intracellular second messenger, cAMP, in eukaryotes. To study the role of cAMP signal transduction in Drosophila development, we have isolated and molecularly characterized mutations of varying severity in the Drosophila PKA gene, DC0. Biochemical measurements indicate that DC0 is either the sole or the major PKA catalytic subunit gene in Drosophila. Adult females heterozygous for a strong and a weak DC0 allele fail to lay eggs and show a striking and novel defect in oogenesis that includes the formation of egg chambers containing multinucleate nurse cells. Females heterozygous for two weak DC0 alleles are fertile but produce offspring showing a variety of defects in embryogenesis, including preblastoderm arrest and alterations in cuticular patterning. Animals zygotically null for DC0 die as morphologically normal first-instar larvae, implying that maternally encoded protein, which perdures for at least 12 hr, suffices for embryogenesis. Animals hemizygous for weak DC0 alleles survive for several days as larvae but grow slowly. Mitotic recombination experiments in the adult eye indicate that the DC0 gene is not required autonomously either for cell viability or normal growth rates. These results argue that cAMP-mediated signal transduction is essential at a variety of stages during the development of a metazoan.