Research Topics
Genomes and Genes | Masaubmi ShibuyaSummaryAffiliation: University of Tokyo Country: Japan Publications
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Publications
Vascular endothelial growth factor (VEGF)-Receptor2: its biological functions, major signaling pathway, and specific ligand VEGF-EMasabumi Shibuya
Division of Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Endothelium 13:63-9. 2006....
Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesisMasabumi Shibuya
Division of Genetics, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
J Biochem Mol Biol 39:469-78. 2006....
Vascular endothelial growth factor-dependent and -independent regulation of angiogenesisMasabumi Shibuya
Department of Molecular Oncology, Tokyo Medical and Dental University, 1 5 45, Yushima, Bunkyo ku, Tokyo, 113 8519, Japan
BMB Rep 41:278-86. 2008..Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy...
Brain angiogenesis in developmental and pathological processes: therapeutic aspects of vascular endothelial growth factorMasabumi Shibuya
Department of Molecular Oncology, Tokyo Medical and Dental University, Japan
FEBS J 276:4636-43. 2009....
Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseasesMasabumi Shibuya
Gakubunkan Institute of Physiology and Medicine, Jobu University, 270 1 Shinmachi, Takasaki, Gunma 370 1393, Japan
J Biochem 153:13-9. 2013..The molecular basis of tumour refractoriness should be determined to improve anti-angiogenic therapy...
Involvement of Flt-1 (VEGF receptor-1) in cancer and preeclampsiaMasabumi Shibuya
Jobu University, Gunma, Japan
Proc Jpn Acad Ser B Phys Biol Sci 87:167-78. 2011..These results indicate a close relationship between abnormal VEGF-block and hypertension/proteinurea. sFlt-1 is an attractive target for the control of preeclampsia...
The overexpression of PKCdelta is involved in vascular endothelial growth factor-resistant apoptosis in cultured primary sinusoidal endothelial cellsT Takahashi
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
Biochem Biophys Res Commun 280:415-20. 2001..TPA was found to downregulate the overexpression of PKCdelta. Thus, we suggest that the VEGF-resistant apoptosis is a new type of endothelial cell death and that PKCdelta is an essential mediator for this process...
Structure and function of VEGF/VEGF-receptor system involved in angiogenesisM Shibuya
Institute of Medical Science, University of Tokyo, Japan
Cell Struct Funct 26:25-35. 2001....
[Angiogenesis, anti-angiogenesis, and tumor suppression]Masabumi Shibuya
Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
Nihon Yakurigaku Zasshi 120:285-94. 2002..In addition to these molecules, unidentified gene products could be specifically involved in certain types of pathological angiogenesis...
Vascular endothelial growth factor receptor-2: its unique signaling and specific ligand, VEGF-EMasabumi Shibuya
Division of Genetics, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
Cancer Sci 94:751-6. 2003..As it directly upregulates tumor angiogenesis, VEGFR-2 is an appropriate target for suppression of solid tumor growth using exogenous antibodies, small inhibitory molecules and in vivo stimulation of the immune system...
Membrane fixation of vascular endothelial growth factor receptor 1 ligand-binding domain is important for vasculogenesis and angiogenesis in miceSachie Hiratsuka
Division of Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
Mol Cell Biol 25:346-54. 2005..These results strongly suggest that the membrane-fixed ligand-binding region of VEGFR1 traps VEGF for the appropriate regulation of VEGF signaling in vascular endothelial cells during early embryogenesis...
Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesisMasabumi Shibuya
University of Tokyo, Institute of Medical Science, 4 6 1 Shirokane dai, Tokyo 108 8639, Japan
Exp Cell Res 312:549-60. 2006..Mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases...
Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesisMasaubmi Shibuya
Division of Genetics, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokane dai, Minato ku, Tokyo, 108 8639, Japan
Angiogenesis 9:225-30; discussion 231. 2006..VEGFR-1 including its soluble form is involved in a variety of human illnesses, making it an important target in the development of new strategies to suppress disease...
Unique signal transduction of the VEGF family members VEGF-A and VEGF-EMasabumi Shibuya
Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
Biochem Soc Trans 37:1161-6. 2009..VEGFE might be more useful than VEGFA for pro-angiogenic therapy...
Professor Hidesaburo Hanafusa: a 50-year quest for the molecular basis of cancerMasabumi Shibuya
Jobu University, Yushima, Bunkyo ku, Tokyo, Japan
J Biochem 146:3-5. 2009....
The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-gamma pathway and partially induces mitotic signals in NIH3T3 fibroblastsT Takahashi
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato ku, Japan
Oncogene 14:2079-89. 1997..These results suggest that the KDR/Flk-1 utilizes cell type-specific signal transduction pathway(s) for MAP kinase activation and the mitotic response in endothelial cells...
A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1)A Yamane
Department of Genetics, University of Tokyo, Japan
Oncogene 9:2683-90. 1994..Therefore two reciprocal communication systems, VEGF-Flt receptor family and HGF-Met receptor, may exist in hepatic tissue...
A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cellsT Takahashi
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
EMBO J 20:2768-78. 2001..These findings strongly suggest that autophosphorylation of Y1175 on KDR is crucial for endothelial cell proliferation, and that this region is a new target for anti-angiogenic reagents...
Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in miceS Hiratsuka
Department of Genetics, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
Proc Natl Acad Sci U S A 95:9349-54. 1998..These results indicate that Flt-1 without tyrosine kinase domain is sufficient to allow embryonic development with normal angiogenesis, and that a receptor tyrosine kinase plays a main biological role as a ligand-binding molecule...
Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOSY Maru
Department of Genetics, University of Tokyo, Japan
Mol Cell Biol 15:835-42. 1995..These data provide evidence that BCR couples the cytoplasmic protein-tyrosine kinase and RAS signaling pathways...
Pulsatile stretch stimulates vascular endothelial growth factor (VEGF) secretion by cultured rat cardiac myocytesY Seko
Graduate School of Medicine, University of Tokyo, Bunkyo ku, Tokyo, Jappan
Biochem Biophys Res Commun 254:462-5. 1999..These data provide the direct evidence that mechanical overload itself can induce VEGF secretion by cardiac myocytes, which may play a role in ameliorating the relative myocardial hypoxia...
The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B proteinN Takeda
Department of Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan
Proc Natl Acad Sci U S A 96:203-7. 1999..The persistent dysfunction of XPB may in part underlie genomic instability in blastic crisis...
Genomic organization of the flt-1 gene encoding for vascular endothelial growth factor (VEGF) receptor-1 suggests an intimate evolutionary relationship between the 7-Ig and the 5-Ig tyrosine kinase receptorsK Kondo
Department of Genetics, University of Tokyo, Japan
Gene 208:297-305. 1998..These results raise the interesting possibility that deletion or insertion mutations of introns in one of these receptor genes took place in the evolutionary generation of the other receptor genes...
Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humansA Sawano
Department of Genetics and Department of Clinical Oncology, Institute of Medical Science, University of Tokyo, Japan
Blood 97:785-91. 2001..These results strongly suggest that Flt-1 is a novel cell surface marker as well as a biologically functional molecule for monocyte-macrophage lineages in humans...
Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesisS Hiratsuka
Department of Genetics, Institute of Medical Science, University of Tokyo, Japan
Cancer Res 61:1207-13. 2001..Thus, Flt-1 has a dual function in angiogenesis, acting in a positive or negative manner in different biological conditions...
Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progressionM Aonuma
New Product Research Laboratories IV, Daiichi Pharmaceutical Co, Ltd, Tokyo, Japan
Int J Exp Pathol 80:271-81. 1999....
An oncogenic form of the Flt-1 kinase has a tubulogenic potential in a sinusoidal endothelial cell lineY Maru
Department of Genetics, Institute of Medical Science, University of Tokyo, Japan
Eur J Cell Biol 79:130-43. 2000..We suppose that matrix ligand-induced integrin signals cooperate with a low level of Flt-1 kinase activity to promote tubulogenic behaviors of endothelial cells in this system...
The tubulogenic activity associated with an activated form of Flt-1 kinase is dependent on focal adhesion kinaseY Maru
Department of Genetics, Institute of Medical Science, University of Tokyo, Japan
Biochim Biophys Acta 1540:147-53. 2001....
The phosphorylated 1169-tyrosine containing region of flt-1 kinase (VEGFR-1) is a major binding site for PLCgammaA Sawano
Institute of Medical Science, University of Tokyo, Minato ku, Tokyo, 108, Japan
Biochem Biophys Res Commun 238:487-91. 1997..These results strongly suggest that Tyr-1169 on Flt-1 is a major binding site for PLCgamma and important for Flt-1 signal transduction within the cell...
The Dbl homology domain of BCR is not a simple spacer in P210BCR-ABL of the Philadelphia chromosomeY Kin
Department of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan
J Biol Chem 276:39462-8. 2001..Although functions of the DH domain remain to be discovered, we propose that the DH domain makes positive contributions to P210BCR-ABL...
Inhibition of protein kinase C delta has negative effect on anchorage-independent growth of BCR-ABL-transformed Rat1 cellsY Kin
Department of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108, Tokyo, Japan
Leuk Res 25:821-5. 2001..Although overexpression of wild type PKC delta did not enhance soft agar colony number by BCR-ABL-transformed Rat1 cells, that of dominant-negative delta isoform reduced it by approximately 40%...
Virally activated Ras cooperates with integrin to induce tubulogenesis in sinusoidal endothelial cell linesY Maru
Department of Genetics, Institute of Medical Science, University of Tokyo, Japan
J Cell Physiol 176:223-34. 1998..These data suggest that the integrin-mediated Ras signals may be necessary but are not sufficient for tubulogenesis and that an artificial expression of v-Ras might substitute for the second signal required in this system...
Isolation and characterization of mouse ovarian surface epithelial cell linesM Kido
Department of Obstetrics and Gynecology, Tokyo University Branch Hospital, Faculty of Medicine, University of Tokyo, Japan
Pathol Res Pract 194:725-30. 1998..The established MOSE cell lines are useful in the molecular analysis of the multistep carcinogenesis of ovarian tissues in humans...
BCR binds to the xeroderma pigmentosum group B proteinY Maru
Department of Genetics, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo, 108 0071, Japan
Biochem Biophys Res Commun 260:309-12. 1999..GST-XPB(1-782) was largely in the nucleus and bound to p62 and BCR. Although the biological significance of the binding remains to be uncovered, BCR binds to the XPB/p62 complex...
TFIIH functions are altered by the P210BCR-ABL oncoprotein produced on the Philadelphia chromosomeY Maru
Department of Genetics, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, 108 0071, Tokyo, Japan
Mutat Res 483:83-8. 2001....
Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activationN Gotoh
Department of Genetics, Institute of Medical Science, University of Tokyo, Japan
Mol Cell Biol 17:1824-31. 1997..These results suggest that Shc activates two distinct signaling pathways, Y317 to Ras/MAPK and Y239 and Y240 to another pathway including Myc, and that both are involved in EGF-induced mitogenic signaling...
DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membraneH Hasegawa
Department of Pathology, National Institute of Health, Toyama, Shinjuku ku, Tokyo, Japan
Mol Cell Biol 16:1770-6. 1996..These results suggest that DOCK180 is a new effector molecule which transduces signals from tyrosine kinases through the CRK adaptor protein...
Amplification and rearrangement of melF/mouse CD43 (leukosialin) gene encoding a highly glycosylated membrane protein gp120 in Friend erythroleukemia cellsY Misawa
Department of Genetics, University of Tokyo, Japan
Oncogene 7:919-26. 1992..These results suggest that melF/mCD43 gene has an important role in progression of leukemic cells in the erythroid lineage and also has a physiological function in normal hematopoiesis...
Tissue-specific expression of rat c-ros-1 gene and partial structural similarity of its predicted products with sev protein of Drosophila melanogasterH Matsushime
Department of Genetics, University of Tokyo, Japan
J Virol 64:2117-25. 1990..On the basis of these results, the c-ros-1 gene appears to be active in the lungs and kidneys and probably in the hearts of rats...
Two species of human CRK cDNA encode proteins with distinct biological activitiesM Matsuda
Department of Pathology, National Institute of Health, Tokyo, Japan
Mol Cell Biol 12:3482-9. 1992..These results demonstrate that the two species of human CRK cDNA encode proteins which differ in their biological activities...
Inhibitory Smad transcription factors protect arterial endothelial cells from apoptosis induced by BMP4M Kiyono
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan
Oncogene 25:7131-7. 2006..Furthermore, intravenous administration of BMP4 into mice caused hemorrhage of capillary EC in brain and lung. These results strongly suggest that BMP4/I-Smads are a novel regulator for the stability of vascular EC...
Unique role of SNT-2/FRS2beta/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathwaysL Huang
Department of Molecular Cellular Oncology and Microbiology, Graduate School, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
Oncogene 25:6457-66. 2006....
Characterization of the promoter region of the human c-kit proto-oncogeneK Yamamoto
Department of Genetics, University of Tokyo
Jpn J Cancer Res 84:1136-44. 1993..In addition, a negative regulatory element(s) is suggested to be involved in the regulation of the c-kit gene expression in mammals...
Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4Y N Williams
Tumor Suppression and Functional Genomics Project, National Cancer Center Research Institute, Chuo Ku, Tokyo, Japan
Oncogene 25:1446-53. 2006..These results suggest that TSLL2 is a new member of the Ig superfamily cell adhesion molecules and is a tumor-suppressor candidate in prostate cancer...
Structure and dual function of vascular endothelial growth factor receptor-1 (Flt-1)M Shibuya
Department of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, 108-8639, Tokyo, Japan
Int J Biochem Cell Biol 33:409-20. 2001..Furthermore, VEGFR-1 is involved in the VEGF-dependent migration and gene expression of monocyte/macrophages. Therefore, VEGFR-1 functions both in a positive and negative manner in different cellular systems and biological conditions...
Altered expression of several genes in highly metastatic subpopulations of a human pulmonary adenocarcinoma cell lineA Gemma
Fourth Department of Internal Medicine, Nippon Medical School, 1 1 5, Sendagi, Bunkyo ku, Tokyo 113 8602, Japan
Eur J Cancer 37:1554-61. 2001..Strategies for inhibiting metastasis of pulmonary adenocarcinoma should be designed accordingly...
Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor proteinY Onishi-Haraikawa
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 8655, Japan
Biochem Biophys Res Commun 288:476-82. 2001..This is a new role for the PI3K regulatory subunit...
A novel mammalian protein kinase gene (mak) is highly expressed in testicular germ cells at and after meiosisH Matsushime
Department of Genetics, University of Tokyo, Japan
Mol Cell Biol 10:2261-8. 1990..These results suggest that the mak gene plays an important role in spermatogenesis...
Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms familyM Shibuya
Department of Genetics, University of Tokyo, Japan
Oncogene 5:519-24. 1990..The expression of the flt gene was strongly suppressed in most of the tumor cell lines examined so far, whereas this mRNA was expressed in a variety of normal tissues of adult rat...
Glucocorticoids increase insulin binding and the amount of insulin-receptor mRNA in human cultured lymphocytesY Shibasaki
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
Biochem J 249:715-9. 1988..The results of this study suggest that cortisol can increase the number of insulin receptors at the cell surface by increasing the amounts of insulin-receptor mRNA and the synthesis de novo of insulin receptors...
Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H-ras genesS Niimi
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan
Br J Cancer 63:237-41. 1991..These results strongly suggest that the expression of the c-myc gene plays a role in the acquisition of drug resistance. The c-myc gene may therefore provide us with an important clue in determining the mechanism of drug resistance...
Unregulated expression of the erythropoietin receptor gene caused by insertion of spleen focus-forming virus long terminal repeat in a murine erythroleukemia cell lineM Hino
Department of Genetics, University of Tokyo, Japan
Mol Cell Biol 11:5527-33. 1991..It is possible that overexpression of EPOR by viral promoter insertion will confer growth advantage to an F-SFFVP-infected erythroid progenitor cell, leading to positive clonal selection through further leukemogenic steps...
A variant of nuclear localization signal of bipartite-type is required for the nuclear translocation of hypoxia inducible factors (1alpha, 2alpha and 3alpha)J C Luo
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
Oncogene 20:1435-44. 2001..Our results suggest that the newly identified NLS is crucial for the functional regulation of HIF family...
Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA)Y Kokubo
Fourth Department of Internal Medicine, Nippon Medical School, 1 1 5 Sendagi, Bunkyo ku, Tokyo 113 8602, Japan
Br J Cancer 92:1711-9. 2005....
Molecular cloning of cDNA encoding rat 2,3-oxidosqualene: lanosterol cyclaseM Kusano
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan
Biol Pharm Bull 18:195-7. 1995..Successive PCRs with all possible combinations of these primers yielded a 178-bp fragment, and based on its sequence full nucleotide sequence of cDNA was obtained by a "rapid amplification of cDNA ends" (RACE) method...
