2004 Fiscal Year Final Research Report Summary
Identification of novel intracellular signaling molecules and clarification of their signal transduction mechanism which regulate abnormal vascular contraction.
| Project/Area Number |
14370014
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KOBAYASHI Sei Yamaguchi University, School of Medicine, Department of Molecular Physiology, Professor, 医学部, 教授 (80225515)
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| Co-Investigator(Kenkyū-buntansha) |
KISHI Hiroko Yamaguchi University, School of Medicine, Department of Molecular Physiology, Assistant Professor, 医学部, 講師 (40359899)
MOGAMI Kimiko Yamaguchi University, School of Medicine, Department of Molecular Physiology, Research Associate, 医学部, 助手 (80263771)
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| Project Period (FY) |
2002 – 2004
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| Keywords | abnormal contraction of vascular smooth muscle / mass spectrometry / calcium-independent contraction / Rho-kinase / sphingolipid / intracellular signal transduction / RNA interference / Src family tyrosine kinase |
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| Research Abstract |
Mortality of vascular diseases is comparable to that of cancer in Japan. It has been reported that C^<2+>-dependent contraction (Ca^<2+>-sensitization) plays a pivotal role in abnormal vascular contraction observed in vascular diseases. The purpose of this study was to identify novel intracellular signaling molecules and to clarify their signal transduction mechanisms.
In the first year, we identified sphingosylphosphorylcholine (SPC) as a novel mediator to induce abnormal vascular contraction. We found that SPC induces Ca^<2+> psensitization through the activation of Src family tyrosine kinase and Rho-kinase in this order
In the second year, in order to find the downstream mediators of Src family tyrosine kinase, we focused on the changes in tyrosine phosphorylation induced by SPC and we succeed in extracting some molecules as downstream mediators of Src family tyrosine kinase.
In the third year, we obtained the following results :
1.We established the cell culture system of vascular smooth muscle which has contractile ability.
2.The siRNA-mediated knock down of Fyn inhibited the SPC-induced contraction of the cultured vascular smooth muscles, indicating the involvement of Fyn in the SPC induced signal transduction.
3.The functional proteomics analysis identified p60, p160, and p200 as the downstream mediators of Fyn.
From these results, we identified Fyn as an intracellular signaling molecule which mediates abnormal vascular contraction. In addition, we propose that Fyn induces abnormal vascular contraction through the tyrosine phosphorylation of p60, p160, and/or p200.
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