| Project/Area Number |
12670133
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Mie University |
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Principal Investigator |
USHIRO Hiroshi Mie Univ., Faculty of Medicine, Associate Professor, 医学部, 助教授 (10151854)
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| Co-Investigator(Kenkyū-buntansha) |
TSUTSUMI Tomonari Mie Univ., Faculty of Medicine, Assistant, 医学部, 助手 (40273370)
KAYAHARA Tatsuro Mie Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (20024705)
NAKANO Katsuma Suzuka Univ. of Medical Science, Faculty of Health Science, Professor and Dean, 保健衛生学部, 教授 (30024623)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Protein kinase / Ste20-related kinase / Cytoskeleton / Actin-binding protein / Cellular stress / Distal convoluted tubule of kidney / Choroid plexus of brain / Gene targeting |
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| Research Abstract |
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.
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