1994 Fiscal Year Final Research Report Summary
Joint Study on the Tumorigenicity of HGF and c-met Receptor
| Project/Area Number |
05044174
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MIZUNO Kensaku Faculty of Science, Kyushu University Associate professor, 理学部, 助教授 (70128396)
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| Co-Investigator(Kenkyū-buntansha) |
VANDE Woude 米国国立がん研究所, フレデリックがんセンター(アメリカ合衆国), センター長
NAKAMURA Toshikazu School of Medicine, Osaka University professor, 医学部, 教授 (00049397)
VANDE WOUDE George f. Frederick Cancer Research and Development Center, National Cancer Institute Dire
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| Project Period (FY) |
1993 – 1994
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| Keywords | Hepatocyte Growth Factor / HGF / c-Met / Oncogene / HGF Converting Enzyme / Tyrosine Kinase / LIM Motif / Receptor |
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| Research Abstract |
Hepatocyte growth factor (HGF) is a pleiotropic factor, which act as a mitogen, motogen, and morphogen for various epithelial cells. The c-Met protooncogene product was identified as the receptor for HGF.In this study, we analyzed the tumorigenicity of HGF and c-Met receptor. Various sarcoma cell lines were found to express high level of c-Met receptor, indicating that the HGF-Met autocrine signaling contributes to the tumorigenic process of sarcoma.HGF converting enzyme, which converts an inactive single-chain precursor (pro-HGF) to a two-chain active form HGF,was purified and identified as a heterodimer protein composed of a 65-kDa heavy chain and a 32-kDa light chain. A synthetic peptide derivative, Ac-Lys-Gln-Leu-Arg-chloromethylketone, containing the sequence of pro-HGF cleavage site strongly inhibited the converting enzyme activity, and the mitogenic activity of pro-HGF.However, this inhibitor could not block the growth of sarcoma cells, probably because of the instability in the conditioned medium. Using the chicken c-sea tyrosine kinase gene (the gene closely related to c-Met) as a probe, we obtained the cDNAs encoding three novel protein kinases, c-Sea, Sky and LIMK.c-Sea is highly related to the c-Met receptor and seems to be a receptor for a HGF-related growth factor. Sky is a novel receptor tyrosine kinase related to Axl/Ufo/Ark. Identification of the ligands for c-Sea and Sky is the subject of ongoing studies. LIMK is a cytoplasmic serine/threonine kinase containing two repeats of LIM/double zinc finger motif at the N-terminus and a protein kinase domain at the C-terminus. LIMK may be involved in the oncogenic process through interactions with other LIM-containing proteins.
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