Novel protein kinases Ark1p and Prk1p associate with and regulate the cortical actin cytoskeleton in budding yeast.

Novel protein kinases Ark1p and Prk1p associate with and regulate the cortical actin cytoskeleton in budding yeast.
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DOI:
10.1083/jcb.144.6.1203
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发表时间:
1999-03-22
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Drubin DG
Drubin DG
中科院分区:
其他
文献类型:
--
作者:
Cope MJ;Yang S;Shang C;Drubin DG

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Ark 1 p(actin regulating kinase 1)被鉴定为结合Sla 2 p的酵母蛋白,Sla 2 p是一种进化上保守的皮质肌动蛋白细胞骨架蛋白。Ark 1 p和第二种酵母蛋白Prk 1 p含有70%相同的NH 2-末端激酶结构域。这些蛋白质与其他六种来自许多生物体的推定激酶一起定义了一个新的蛋白激酶家族,我们将其命名为方舟家族。缺乏Ark 1 p和Prk 1 p导致形成大的细胞质肌动蛋白团块和细胞生长的严重缺陷。这些缺陷被野生型挽救,但不能被激酶死亡的蛋白质版本挽救。Ark 1 p或Prk 1 p水平升高导致了一些肌动蛋白和细胞形态缺陷,而这些缺陷在激酶死亡版本过度表达时没有观察到。Ark 1 p和Prk 1 p被证明定位于肌动蛋白皮质斑块,使这两种激酶成为第一个被证明是斑块成分的信号蛋白。这些结果表明,Ark 1 p和Prk 1 p可能是控制肌动蛋白斑块组织和功能的信号通路的下游效应子。此外,双突变体分析的结果表明,Ark 1 p和Prk 1 p的功能重叠,但不同的途径,调节皮质肌动蛋白细胞骨架。
Ark1p (actin regulating kinase 1) was identified as a yeast protein that binds to Sla2p, an evolutionarily conserved cortical actin cytoskeleton protein. Ark1p and a second yeast protein, Prk1p, contain NH2-terminal kinase domains that are 70% identical. Together with six other putative kinases from a number of organisms, these proteins define a new protein kinase family that we have named the Ark family. Lack of both Ark1p and Prk1p resulted in the formation of large cytoplasmic actin clumps and severe defects in cell growth. These defects were rescued by wild-type, but not by kinase-dead versions of the proteins. Elevated levels of either Ark1p or Prk1p caused a number of actin and cell morphological defects that were not observed when the kinase-dead versions were overexpressed instead. Ark1p and Prk1p were shown to localize to actin cortical patches, making these two kinases the first signaling proteins demonstrated to be patch components. These results suggest that Ark1p and Prk1p may be downstream effectors of signaling pathways that control actin patch organization and function. Furthermore, results of double-mutant analyses suggest that Ark1p and Prk1p function in overlapping but distinct pathways that regulate the cortical actin cytoskeleton.
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