2001 Fiscal Year Final Research Report Summary
Activating mechanisms of platelet GPIIb-IIIa complex by the interaction of intracellular proteins
| Project/Area Number |
11671001
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
FUJIMOTO Tetsuro School of Medicine, Hiroshima Univ., Associate Professor, 医学部, 助教授 (00221549)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOMURA Takeshi University Hospital, Hiroshima Univ., Assistant, 医学部・附属病院, 助手 (20263741)
FUJIMURA Kingo School of Medicine, Hiroshima Univ., Professor, 医学部, 教授 (80034114)
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| Project Period (FY) |
1999 – 2001
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| Keywords | platelets / GPIIb-IIIa complex / affinity modulation / β3-endonexin / CD98 / IAP / two hybrid system / FBLP-1 |
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| Research Abstract |
In order to determine the activating mechanisms of platelet GPIIb-IIIa complex, the role of several associated proteins was analyzed. β3-endonexin activated GPIIb-IIIa complex. However it did not effectively localize near the plasma membrane since it was a nuclear protein. CD98 activated GPIIb-IIIa complex during platelet and cell adhesion. IAP strongly activated GPIIb-IIIa complex and induced soluble ligand bindings only when it interacted with C-terminal domain of thrombospondin. Several cytoskeletal proteins including talin and filamin influenced the function of GPIIb-IIIa complex. To know these downstream pathways, proteins that bind to filamins were identified by yeast two hybrid screening. One clone was a novel cDNA, which encoded 375 amino acids and 45kDa protein. Deduced amino acid sequence showed that it contained a proline-rich domain at its N-terminal half and two LIM domains at C-terminus. We therefore, named it as FBLP-1 (Filamin Binding LIM Protein-1). Subcellular localization analysis showed that FBLP-1 co-localized with stress fibers, which stretched from focal adhesions containing GPIIb-IIIa complex. The cells, which over expressed FBLP-1, spread more effectively than the cells which did not express FBLP-1, suggesting that FBLP-1 plays a significant role on platelet adhesion. Further investigation of these associated proteins would clarify the activating mechanisms of platelet GPIIb-IIIa complex.
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Research Products
(15 results)
