2006 Fiscal Year Final Research Report Summary
Study on_the protein-protein interaction regulating the function of amino acid transporters
| Project/Area Number |
17590226
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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 |
General pharmacology
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| Research Institution | Kyorin University |
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Principal Investigator |
KANAI Yoshikatsu Kyorin University, School of Medicine, Professor (60204533)
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| Co-Investigator(Kenkyū-buntansha) |
ANZAI Naohiko Kyorin University, School of Medicine, Instructor (70276054)
HIRATA Taku Kyorin University, School of Medicine, Instructor (60372918)
UENO Takeshi Kyorin University, School of Medicine, Instructor (20406979)
CHAIROUNGDUA A 杏林大学, 医学部, 助手
KIMIURA Toru Kyorin University, School of Medicine, Instructor (60383668)
HOSOYAMADA Makoto Kyorin University, School of Medicine, Instructor (00291659)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Pharmacology / transporter / membrane protein / Protein-protein interaction / amino acid / membrane targeting / Functional regulation / scaffold protein |
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| Research Abstract |
Heterodimeric amino acid transporters are formed by disulfide bonding of a twelve-membrane spanning protein (catalytic subunit) and a single membrane spanning protein (regulatory subunit). We have performed BLAST searches of human and mouse genome data bases using amino acid sequences of LAT1, BAT1 and CAT1 as queries. We have found 5 new genes, SLC7-N1-5, as new members of SLC7 family. By searching EST (expressed sequence tag) data bases, we have concluded that two of them (SLC7 N4 and SLC7 N5) are pseudogenes, because they never appear in EST data bases. SLC7 -N1 possesses 12 transmembrane domains and is supposed to be a catalytic subunit of heterodimeric amino acid transporters. We have named it AGT 1. AGT 1 protein is found on the basolateral membrane of proximal and distal tubules of mouse kidney. Because AGT 1 is supposed to be linked with unknown regulatory subunit, we have generated fusion proteins in which AGT 1 is connected with known regulatory subunits 4F2hc or rBAT and expressed them in Xenopus oocytes. The fusion proteins appear on the plasma membrane and exhibit the transport of acidic amino acids. SLC7 N2 possesses 14 transmembrane domains and exhibits particularly high affinity to arginine, thus we named it CATS (cationic amino acid transporter 5). CAT5 is expressed in the syncytio-trophoblast of mouse placenta and supposed to mediate transport of amino acids through the placental bather as well as to supply placental cells with arginine as a precursor of NO synthesis. SLC7 N3 also possesses 14 transmembrane domains and transports small neutral amino acids as well as small basic amino acids, thus we have named it y^+Asc-1. In this study, the function of all the members of heterodimeric amino acid transporter family has been revealed. The results of this study would provide essential information to establish the basis for the genome-wide analyses of diseases or pathological conditions and facilitate drug design targeting the transporters of interest.
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Research Products
(35 results)
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[Journal Article] Expression of LAT1 predicts risk of progression of transitional cell carcinoma of the upper urinary tract2007
Author(s)
Nakanishi, K, Ogata, S, Matsuo, H, Kanai, Y, Endou, H, Hiroi, S, Tominaga, S, Aida, S, Kasamatsu, H, Kawai, T
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dual-color imaging of nuclear-cytoplasmic dynamics, viability, and proliferation of cancer cells in the portal vein area2006
Author(s)
Tsuji K, Yamauchi K, Yang M, Jiang P, Bouvet M, Endo H, Kanai Y, Yamashita K, Moossa AR, Hoffman RM
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Journal Title
Cancer Res 66
Pages: 303-306
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Localization of Ang-1,-2,Tie-2,and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis2006
Author(s)
Wakui S, Yokoo K, Muto T, Suzuki Y, Takahashi H, Furusato M, Hano H, Endou H, Kanal Y
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Journal Title
Lab Invest 86
Pages: 1172-1184
Description
「研究成果報告書概要(和文)」より
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[Journal Article] LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung2006
Author(s)
Nakanishi, K, Matsuo, H, Kanai, Y, Endou, H, Hiroi, S, Tominaga, S, Mukai, M, Ikeda, E, Ozeki, Y, Aida, S, Kawai, T
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Journal Title
Virchows Arch 448
Pages: 142-150
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prenatal 3, 3', 4, 4', 5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7, 12-d methylbenz[a]anthracene2006
Author(s)
Wakui, S, Yokoo, K, Takahashi, H, Muto, T, Suzuki, Y, Kanai, Y, Hano, H, Furusato, M, Endou, H
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Journal Title
Toxicol Appl Pharmacol 210
Pages: 200-211
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter2006
Author(s)
Shigeta, Y, Kanai, Y, Chairoungdua, A, Ahmed, N, Sakamoto, S, Matsuo, H, Kim, DK, Fujimura, M, Anzai, N, Mizoguchi, K, Ueda, T, Akakura, K, Ichikawa, T, Ito, H, Endou, H
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Journal Title
Kidney Int 69
Pages: 1198-1206
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The PDZ domain protein PDZK1 interacts with human peptide transporter PEPT2 and enhances its transport activity2006
Author(s)
Noshiro, R, Anzai, N, Sakata, T, Miyazaki, H, Terada, T, Shin, HJ, He, X, Miura, D, Inui, K, Kanai, Y, Endou, H
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Journal Title
Kidney Int 70
Pages: 275-282
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction2006
Author(s)
Brandoni, A, Villar, SR, Picena, JC, Anzai, N, Endou, H, Torres, AM
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Journal Title
Hepatology 43
Pages: 1092-1100
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Human vascular smooth muscle cells express a urate transporter2006
Author(s)
Price, KL, Sautin, YY, Long, DA, Zhang, L, Miyazaki, H, Mu, W, Endou, H, Johnson, RJ
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Journal Title
J Am Soc Nephrol 17
Pages: 1791-1795
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Treatment effects and predictors of a 24-week course of interferon alpha-2b plus ribavirin combination therapy for patients with chronic hepatitis C2006
Author(s)
Tomimatsu, M, Aizawa, Y, Chuganji, Y, Ishizuka, H, Fujita, Y, Aizawa, R, Abe, H, Matsuda, T, Itou, Y, Nakanishi, H, Ushiyama, H, Higuchi, T, Fujimoto, T, Endou, H, Iga, D, Ohta, K, Kuroda, H
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Journal Title
J Gastroenterol Hepatol 21
Pages: 1177-1183
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors2006
Author(s)
Nawashiro, H, Otani, N, Shinomiya, N, Fukui, S, Ooigawa, H, Shima, K, Matsuo, H, Kanai, Y, Endou, H
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Journal Title
Mt. J Cancer 119
Pages: 484-492
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Differential expression and functional characterization of system L amino acid transporters in human normal osteoblast cells and osteogenic sarcoma cells2006
Author(s)
Kim, SG, Kim, HH, Kim, HK, Kim, CH, Chun, HS, Kanai, Y, Endou, H, Kim, do, K
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Journal Title
Anticancer Res 26
Pages: 1989-1996
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Fluorine-18-α-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer:A clinicopathological study
Author(s)
Kaua, K, Oriuchi, N, Otam, Y, Shimizu, K, Tanaka, S, Imai, H, Yanagitani, N, Sunaga, N, Hisada, T, Ishizuka, T, Dobashi, K, Kanai, Y, Endou, H, Nakajima, T, Endo, K, Mori, M
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Journal Title
Clin.Cancer Res (in press)
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells
Author(s)
Kobayashi, K, Ohnishi, A, Promsuk, J, Kanai, Y, Endou, H, Shiokawa, Y, Nagane, M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Fluorine-18- α -methyltyrosine positron emission tomography for diagnosis and staging of lung cancer : A clinicopathological study
Author(s)
Kaira, K, Oriuchi, N, Otani, Y, Shimizu, K, Tanaka, S, Imai, H, Yanagitani, N, Sunaga, N, Hisada, T, Ishizuka, T, Dobashi, K, Kanai, Y, Endou, H, Nakajima, T, Endo, K, Mori, M
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Journal Title
Clin. Cancer Res (in press)
Description
「研究成果報告書概要(欧文)」より
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