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蛋白激酶 D 在 …… 的发育和存活中是可有可无的。

Protein Kinase D Is Dispensable for Development and Survival of .

机构信息

Universität Hohenheim, Institut für Genetik (240A), Garbenstr. 30, 70599 Stuttgart, Germany.

Universität Hohenheim, Institut für Genetik (240A), Garbenstr. 30, 70599 Stuttgart, Germany

出版信息

G3 (Bethesda). 2019 Aug 8;9(8):2477-2487. doi: 10.1534/g3.119.400307.

Abstract

Members of the Protein Kinase D (PKD) family are involved in numerous cellular processes in mammals, including cell survival after oxidative stress, polarized transport of Golgi vesicles, as well as cell migration and invasion. PKD proteins belong to the PKC/CAMK class of serine/threonine kinases, and transmit diacylglycerol-regulated signals. Whereas three PKD isoforms are known in mammals, contains a single PKD homolog. Previous analyses using overexpression and RNAi studies indicated likewise multi-facetted roles for PKD, including the regulation of secretory transport and actin-cytoskeletal dynamics. Recently, involvement in growth regulation has been proposed based on the hypomorphic d allele. We have generated null alleles that are homozygous viable without apparent phenotype. They largely match control flies regarding fertility, developmental timing and weight. Males, but not females, are slightly shorter lived and starvation sensitive. Furthermore, migration of pole cells in embryos and border cells in oocytes appears normal. mutants tolerate heat, cold and osmotic stress like the control but are sensitive to oxidative stress, conforming to the described role for mammalian PKDs. A candidate screen to identify functionally redundant kinases uncovered genetic interactions of with , and mutants, further supporting the role of PKD in oxidative stress response, and suggesting its involvement in starvation induced autophagy and regulation of cytoskeletal dynamics. Overall, PKD appears dispensable for fly development and survival presumably due to redundancy, but influences environmental responses.

摘要

蛋白激酶 D(PKD)家族成员参与哺乳动物的许多细胞过程,包括氧化应激后的细胞存活、高尔基体小泡的极化运输以及细胞迁移和侵袭。PKD 蛋白属于 PKC/CAMK 类丝氨酸/苏氨酸激酶,并传递二酰基甘油调节的信号。虽然哺乳动物中有三种 PKD 同工型,但 只包含一个 PKD 同源物。以前的过表达和 RNAi 研究分析表明, PKD 具有多方面的作用,包括调节分泌运输和肌动蛋白细胞骨架动力学。最近,基于弱等位基因 d,提出了它参与生长调节的假说。我们已经生成了纯合子可育但无明显表型的 缺失突变体。它们在生育能力、发育时间和体重方面与对照品系基本一致。雄性,而不是雌性,寿命略短,对饥饿敏感。此外,胚胎中的极细胞迁移和卵母细胞中的边缘细胞迁移似乎正常。 突变体对热、冷和渗透压应激的耐受性与对照品系相同,但对氧化应激敏感,这与描述的哺乳动物 PKDs 的作用一致。一个鉴定功能冗余激酶的候选筛选发现 与 、 和 突变体之间存在遗传相互作用,进一步支持了 PKD 在氧化应激反应中的作用,并表明其参与饥饿诱导的自噬和细胞骨架动力学的调节。总体而言,PKD 似乎对果蝇的发育和生存不是必需的,可能是由于冗余,但会影响环境反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6bf/6686927/a34d197e0ff7/2477f1.jpg

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