| Project/Area Number |
09670150
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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 | GIFU UNIVERSYTI |
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Principal Investigator |
BANNO Yoshiko SCHOOL OF MEDICINE,GIFU UNIVERSITY LECTURER, 医学部, 講師 (50116852)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Shigeru SCHOOL OF MEDICINE,GIFU UNIVERSYTI ASSOCIATE PROFESSOR, 医学部, 助教授 (60188935)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Human platelet / Phospholipase C / Integrin signaling / Gbetagamma subunit / 血小板 / インテグリンGPIIb / IIIa / PI-PLC / チロシンリン酸化 / 接着 |
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| Research Abstract |
It has been known that the platelet integrin alpha_<IIb>beta_3 is involved in platelet aggregation and adhesion. When platelets are stimulated by agonists, intracellular signal transduction can be activated, leading to a conformational change in the extracellular domains of integrin alpha_<IIb>beta_3 that increases its affinity for adhesive ligands, for example fibrinogen, resulting in platelet aggregation. Recent study has demonstrated that Galphaq is important in platelet aggregation induced by all agonists and Gi or G12/13 are involved in shape change. To investigate a role of phospholipase C (PLC) isozymes in the integrin alpha_<IIb>beta_3-mediated signaling, their location was examined in thrombin-activated human platelets, revealing different regulation of their translocation to the cytoskeleton (CSK). PLCbeta3b (l4OkDa) was present only in the cytosolic fraction and thrombin stimulation caused a rapid and transient translocation of PLCbeta3(a, b) in the reorganized CSK.The translocation to CSK of both PLCbeta3(a, b), but not PLCbeta2 was dependent on integrin alpha_<IIb>beta_3-mediated aggregation. The integrin alpha_<IIb>beta_3-mediated cytoskeletal association of PLCbeta3 was truncated by calpain. The truncated PLCbeta3 was activated G protein betagamma subunits. The human platelet Gi2 and Gq were consisted from beta1gamma5. No significant differences. for PLCbeta3 activation were not observed among various Gbetagamma subunits. These results suggested that combination of agonist-induced PLCbeta2/3 activation via Gqalpha and integrin-mediated PLCbeta3 activation via Gbetagamma may be important in platelet aggregation and adhesion.
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