| Project/Area Number |
13671066
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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 |
Hematology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
SATO Yutaka Yamaguchi University Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (20253156)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toru Yamaguchi University Hospital Clinical Resident, 医学部附属病院, 医員(臨床)
YUJIRI Toshiaki Yamaguchi University Hospital, Assistant Professor, 医学部附属病院, 講師 (80346551)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | MEK kinase 1 / Focal adhesion kinase / Insulin receptor substrate 1 / MEKK1 / FAK / IRS-1 / MEKK |
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| Research Abstract |
The MEK Kinase (MEKK) family members are regulated by a diverse array of extracellular stimuli ranging from growth factors to DNA damaging stimuli and so are important for the cell to sense exposure to various environmental stimuli. MEKK1 has been shown to contribute to the regulation of cell migration, while focal adhesion kinase (FAK) is a major player involved in both cell migration and integrin signaling. We show that MEKK1 and FAK are co-immunoprecipitated from mouse fibroblasts. Moreover, the association between MEKK1 and FAK appears to be physiologically relevant, as it is enhanced by treatment with epidermal growth factor (EGF). Targeting FAK to the membrane also enhanced its association with MEKK1, indicating MEKK1 to be localized to a membrane-related subcellular domain, perhaps focal adhesions. Interestingly, expression of insulin receptor substrate-I (IRS-1) was diminished in MEKK1-deficient fibroblasts, which is similar to an earlier finding in FAK-deficient fibroblasts. Insulin-like growth factor 1 (IGF-I)-induced ERK activation was also diminished in MEKK1-deficient cells, but PI3K/Akt activation was not. Although integrin reportedly regulates the transcription of the IRS-1 gene via FAK-mediated JNK activation, no impairment of fibronectin-stimulated activation of FAK, ERK or JNK was observed in MEKK1 -deficient cells. Reconstitution of MEKK1 expression restored IRS-1 expression as well as IGF-1-induced ERK activation. Taken together, these findings indicate that MEKK1 interacts with FAK in focal adhesions and regulates IRS-1 expression.
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