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Function of Protein Kinase PASK enriched in Transporting Epithelia

富含蛋白激酶 PASK 的上皮运输功能

基本信息

批准号：
12670133
负责人：
USHIRO Hiroshi
金额：
$ 2.18万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670133/
关键词：
Protein kinase Ste20-related kinase Cytoskeleton Actin-binding protein Cellular stress Distal convoluted tubule of kidney Choroid plexus of brain Gene targeting

项目摘要

PASK is a Ste20-related protein kinase enriched in adrenal zona glomerulosa cells and transporting epithelia such as brain choroid plexus and gastric parietal cells. The molecular function and physiological roles of PASK have been investigated in this study, and we have obtained the following results :1. PASK associates actin and tubulin in vivo, and in its kinase domain has F-actin-binding activity. In cultured cells, PASK translocates from the cytosol to cytoskeleton upon stimulation by cellular stresses like heat shock and hypersonic NaCl. These results suggest that PASK is involved in the regulation of cytoskeleton during responses to cellular stresses.The C-terminal non-catalytic domain binds cytoskeleton when cells are exposed to celluar stresses, while the kinase domain binds cytoskeleton regardless exposure to the celluar stresses. These results suggest that PASK binds cytoskeleton through its kinase domain to actin cytoskeleton and through the C-terminal domain to cytoskeleton via non-actin protein(s).2. PASK-deficient mice generated by targeted disruption of the PASK gene exhibit reduced fertility and shows anomalies in the reproductive organs : PASK deficient males have testes that were 77 % of the normal size and the uterine of mutant females is 2- to 3-fold larger than the wild-type. Portions of the seminiferous tubules of sterile mutant males contain no spermatids, while such tubules are rare in the fertile mutants. These results suggest that PASK is involved in the reproduction. The mechanisms by which PASK deletion affects the reproduction, including the cause of anomalies in the mutant reproductive organs, are currently under investigation in this laboratory.

PASK是一种Ste 20相关的蛋白激酶，在肾上腺皮质球状细胞和运输上皮如脑脉络丛和胃壁细胞中富集。本研究对PASK的分子功能和生理作用进行了初步探讨，主要结果如下：1。PASK在体内将肌动蛋白和微管蛋白结合，并且在其激酶结构域中具有F-肌动蛋白结合活性。在培养的细胞中，PASK在受到细胞应激如热休克和高超声NaCl的刺激时从细胞溶质易位到细胞骨架。这些结果表明，PASK参与了细胞应激反应中细胞骨架的调节，C端非催化结构域在细胞应激时与细胞骨架结合，而激酶结构域在细胞应激时与细胞骨架结合。这些结果表明，PASK通过其激酶结构域与肌动蛋白骨架结合，并通过C端结构域与非肌动蛋白骨架结合.通过靶向破坏PASK基因产生的PASK缺陷型小鼠表现出生育力降低，并显示生殖器官异常：PASK缺陷型雄性的睾丸为正常大小的77%，突变型雌性的子宫比野生型大2- 3倍。不育突变体雄性的部分曲细精管不含精子细胞，而这种曲细精管在可育突变体中是罕见的。这些结果表明PASK参与生殖。PASK缺失影响生殖的机制，包括突变生殖器官异常的原因，目前正在本实验室进行研究。