2003 Fiscal Year Annual Research Report

ゲノム情報を用いたヘテロ二量体型アミノ酸トランスポーターファミリーの全容の解明

Research Project

Project/Area Number	14570085
Research Institution	Kyorin University
Principal Investigator	金井好克杏林大学, 医学部, 教授 (60204533)
Co-Investigator(Kenkyū-buntansha)	安西尚彦杏林大学, 医学部, 助手 (70276054) 入部雄司杏林大学, 医学部, 助手 (20348618)
Keywords	アミノ酸 / トランスポーター / 細胞膜輸送 / ゲノム / ポストゲノム / SLC / ヘテロ二量体型タンパク質 / 輸送体
Research Abstract	本研究は、研究代表者らが分子実体解明を推進してきたヘテロ二量体型アミノ酸トランスポーターファミリーのゲノム上の全メンバーを明らかにし、その機能を同定することにより、ヘテロ二量体型アミノ酸トランスポーターファミリーの全容を明らかにすることを目的として行われている。ヘテロ二量体型アミノ酸トランスポーターファミリーは、トランスポーターの本体である12回膜貫通型のタンパク質(主サブユニット)と、1回膜貫通型の補助因子(補助サブユニット)が、ジスルフィド結合によって連結することにより形成される。主サブユニットはSLC(solete carrier)7ファミリーのヘテロ二量体型アミノ酸トランスポーターファミリーのに属する。平成15年度は、前年度に新たに同定した4種の未同定の遺伝子の機能及び発現局在の解析を行った。SLC7-N2は、塩基性アミノ酸トランスポーターCAT1〜4と比較的高い相同性を有し、特にアルギニンに対して親和性の高いNa^+非依存的な塩基性アミノ酸輸送活性を示したため、CAT5(cationic amino acid transporter 5)と命名した。CAT5は主に胎盤に発現し、免疫組織学的検討により合胞体絨毛細胞に存在することが明らかになった。従ってCAT5については、一酸化窒素(NO)生成の基質としてのアルギニンの細胞への供給とともに、塩基性アミノ酸の胎盤関門透過における役割が示唆された。また、SLC7のメンバーのAsc-2及びAGT1は、その補助サブユニットが未同定であるが、これを明らかにするためにグルタチオン-S-トランスフェラーゼとの融合タンパク質を作製し、そのcDNAをマウス胚に注入することにより、融合タンパク質を強制発現するトランスジェニックマウスを作製することができ、今後の新しい課題への展開が考えられる。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Shikano, N, Kanai, Y, Kawai, K, Ishikawa, N, Endou, H.: "Characterization of 3-[(125)I]iodo-alpha-methyl-L-tyrosine transport via human L-type amino acid transporter 1."Nucl.Med.Biol.. 30. 31-37 (2003)
[Publications] Shikano, N, Kanai, Y, Kawai, K, Inatomi, J, Kim, DK, Ishikawa, N, Endou: "Isoform selectivity of 3-125I-iodo-alpha-methyl-L-tyrosine membrane transport in human L-type amino acid transporters."J.Nucl.Med.. 44. 244-246 (2003)
[Publications] Muto, T, Takasaki, S, Takahashi, T, Hano, H, Kanai, Y, Wakui, S, Endou, H, Furusato, M: "Initial changes of hepatic glycogen granules and glycogen phosphorylase a after exposure to 7,12-dimethylbenz[a]anthracene in rats."J.Toxicol.Pathol.. 16. 153-160 (2003)
[Publications] Jutabha, P, Kanai, Y, Hosoyamada, M, Chairoungdua, A, Kim, DK, Iribe, Y, Babu, E, Kim, JY, Anzai, N, Chatsudthipong, V, Endou, H: "Identification of a novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule."J.Biol.Chem.. 278. 27930-27938 (2003)
[Publications] Babu, E, Kanai, Y, Chairoungdua, A, Ki, DK, Iribe, Y, Tangtrongsup, S, Jutabha, P, Li, Y, Ahmed, N, Sakamoto, S, Anzai, N, Endou, H: "Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters."J.Biol.Chem.. 278. 43838-43845 (2003)
[Publications] Yoon, JH, Kim, YB, Kanai, Y, Endou, H, Kim, DK: "Sequential increases in 4F2hc expression during DMBA-induced hamster buccal pouch carcinogenesis."Anticancer Res.. 28. 1-17 (2003)
[Publications] Muto, T, Watanabe, T, Moto, M, Okamura, M, Kashida, Y, Kanai, Y, Mitsumori, K, Endou, H: "Time course of expression of 7,12-dimethylbenz[a]anthracene-induced CYP1A1 and CYP1B1 mRNA and protein in rat liver."J.Toxicol.Pathol.. 16. 287-290 (2003)
[Publications] Sakata, T, Anzai, N, Shin, HJ, Noshiro, R, Hirata, T, Yokoyama, H, Kanai, Y, Endou, H: "Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions."Biochem.Biophys.Res.Commun.. 313. 789-793 (2004)
[Publications] Shikano N, Kanai Y, Kawai K, Ishikawa N, Endou H: "Transport of 99mTc-MAG3 via rat renal organic anion transporter 1."J Nucl Med.. 45. 80-85 (2004)
[Publications] Matsuo, H, Kanai, Y, Tokunaga, M, Nakata, T, Chairoungdua, A, Ishimine, H, Tsukada, S, Ooigawa, H, Nawashiro, H, Kobayashi, Y, Fukuda, J, Endou, H: "High affinity D- and L-serine transporter Asc-1 : Cloning and dendritic localization in the rat cerebral and cerebellar cortices."Neurosci.Lett.. 358(2). 123-126 (2004)
[Publications] Yoon JH, Kim YB, Kim MS, Park JC, Kook JK, Jung HM, Kim SG, Yoo H, Ko YM, Lee SH, Kim BY, Chun HS, Kanai Y, Endou H, Kim do K.: "Expression and functional characterization of the system L amino acid transporter in KB human oral epidermoid carcinoma cells."Cancer Lett.. 205. 215-226 (2004)
[Publications] Park JC, Kim YB, Yoon JH, Kim HJ, Kim SM, Kanai Y, Endou H, Kim DK.: "Preferential Expression of L-type Amino Acid Transporter 1 in Ameloblasts During Rat Tooth Development."Anat Histol Embryol.. 33. 119-124 (2004)
[Publications] Ekaratanawong S, Anzai N, Jutabha P, Miyazaki H, Noshiro R, Takeda M, Kanai Y, Sophasan S, Endou H: "Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules."J.Pharniacol.Sci.. 94. 297-304 (2004)
[Publications] Kanai, Y, Endou, H: "Functional properties of multispecific amino acid transporters and their implications to transporter-mediated toxicity."J.Toxicol.Sci.. 28. 1-17 (2003)
[Publications] 金井好克: "アミノ酸輸送体の多様性:アミノ酸代謝異常症の分子基盤"Molecular Medicine. 40. 782-790 (2003)
[Publications] Verrey, F, Closs, EI, Wagner, CA, Palacin, M, Endou, H, Kanai, Y: "CATs and HATs : the SLC7 family of amino acid transporters."Pflugers Arch.. 447. 532-542 (2004)
[Publications] Palacin, M, Kanai, Y: "The ancillary proteins of HATs : SLC3 family of amino acid transporters."Pflugers Arch.. 447. 490-494 (2004)
[Publications] Kanai, Y, Heidiger, MA: "The Glutamate and Neutral Amino Acid Transporter Family : Physiological and Pharmacological Implications."Pflugers Arch.. 447. 469-479 (2004)
[Publications] Kanai, Y, Heidiger, MA: "The glutamate and neutral amino acid transporter family : physiological and pharmacological implications."Eur.J.Pharmacol.. 479. 237-247 (2003)
[Publications] Kanai Y, Endou H: "Molecular characteristics and physiological and pharmacological implications of heterodimeric amino acid transporters. In Topics in Current Genetics : Molecular Mechanisms Controlling Transmembrane Transport. ed. Stefan Hohmann"Springer, Heidelberg(in press).

2003 Fiscal Year Annual Research Report

ゲノム情報を用いたヘテロ二量体型アミノ酸トランスポーターファミリーの全容の解明

Principal Investigator

金井 好克 杏林大学, 医学部, 教授 (60204533)

Research Products

[Publications] Shikano, N, Kanai, Y, Kawai, K, Ishikawa, N, Endou, H.: "Characterization of 3-[(125)I]iodo-alpha-methyl-L-tyrosine transport via human L-type amino acid transporter 1."Nucl.Med.Biol.. 30. 31-37 (2003)

[Publications] Shikano, N, Kanai, Y, Kawai, K, Inatomi, J, Kim, DK, Ishikawa, N, Endou: "Isoform selectivity of 3-125I-iodo-alpha-methyl-L-tyrosine membrane transport in human L-type amino acid transporters."J.Nucl.Med.. 44. 244-246 (2003)

[Publications] Muto, T, Takasaki, S, Takahashi, T, Hano, H, Kanai, Y, Wakui, S, Endou, H, Furusato, M: "Initial changes of hepatic glycogen granules and glycogen phosphorylase a after exposure to 7,12-dimethylbenz[a]anthracene in rats."J.Toxicol.Pathol.. 16. 153-160 (2003)

[Publications] Yoon, JH, Kim, YB, Kanai, Y, Endou, H, Kim, DK: "Sequential increases in 4F2hc expression during DMBA-induced hamster buccal pouch carcinogenesis."Anticancer Res.. 28. 1-17 (2003)

[Publications] Muto, T, Watanabe, T, Moto, M, Okamura, M, Kashida, Y, Kanai, Y, Mitsumori, K, Endou, H: "Time course of expression of 7,12-dimethylbenz[a]anthracene-induced CYP1A1 and CYP1B1 mRNA and protein in rat liver."J.Toxicol.Pathol.. 16. 287-290 (2003)

[Publications] Sakata, T, Anzai, N, Shin, HJ, Noshiro, R, Hirata, T, Yokoyama, H, Kanai, Y, Endou, H: "Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions."Biochem.Biophys.Res.Commun.. 313. 789-793 (2004)

[Publications] Shikano N, Kanai Y, Kawai K, Ishikawa N, Endou H: "Transport of 99mTc-MAG3 via rat renal organic anion transporter 1."J Nucl Med.. 45. 80-85 (2004)

[Publications] Park JC, Kim YB, Yoon JH, Kim HJ, Kim SM, Kanai Y, Endou H, Kim DK.: "Preferential Expression of L-type Amino Acid Transporter 1 in Ameloblasts During Rat Tooth Development."Anat Histol Embryol.. 33. 119-124 (2004)

[Publications] Ekaratanawong S, Anzai N, Jutabha P, Miyazaki H, Noshiro R, Takeda M, Kanai Y, Sophasan S, Endou H: "Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules."J.Pharniacol.Sci.. 94. 297-304 (2004)

[Publications] Kanai, Y, Endou, H: "Functional properties of multispecific amino acid transporters and their implications to transporter-mediated toxicity."J.Toxicol.Sci.. 28. 1-17 (2003)

[Publications] 金井好克: "アミノ酸輸送体の多様性:アミノ酸代謝異常症の分子基盤"Molecular Medicine. 40. 782-790 (2003)

[Publications] Verrey, F, Closs, EI, Wagner, CA, Palacin, M, Endou, H, Kanai, Y: "CATs and HATs : the SLC7 family of amino acid transporters."Pflugers Arch.. 447. 532-542 (2004)

[Publications] Palacin, M, Kanai, Y: "The ancillary proteins of HATs : SLC3 family of amino acid transporters."Pflugers Arch.. 447. 490-494 (2004)

[Publications] Kanai, Y, Heidiger, MA: "The Glutamate and Neutral Amino Acid Transporter Family : Physiological and Pharmacological Implications."Pflugers Arch.. 447. 469-479 (2004)

[Publications] Kanai, Y, Heidiger, MA: "The glutamate and neutral amino acid transporter family : physiological and pharmacological implications."Eur.J.Pharmacol.. 479. 237-247 (2003)

[Publications] Kanai Y, Endou H: "Molecular characteristics and physiological and pharmacological implications of heterodimeric amino acid transporters. In Topics in Current Genetics : Molecular Mechanisms Controlling Transmembrane Transport. ed. Stefan Hohmann"Springer, Heidelberg(in press).

金井好克杏林大学, 医学部, 教授 (60204533)