1995 Fiscal Year Annual Research Report

増殖因子レセプターによるシグナル伝達と複製開始の制御に関する共同研究

Research Project

Project/Area Number	07044230
Research Institution	The University of Tokyo
Principal Investigator	新井賢一東京大学, 医科学研究所, 教授 (00012782)
Co-Investigator(Kenkyū-buntansha)	LEES Emma DNAX研究所, 細胞シグナリング研究部, 主任研究員新井直子 DNAX研究所, 細胞シグナリング研究部, 副部長 MASUDA Esteb DNAX研究所, 細胞シグナリング研究部, 研究員 YSSEL Hans DNAX研究所, ヒト免疫学研究部, 主任研究員 SHOMAI Josep ヘブライ大学, 医学部, 教授佐藤憲子東京大学, 医科学研究所, 教務職員小谷野葉峰子 (中川葉) 東京大学, 医科学研究所, 教務職員 (80270908) 渡辺すみ子東京大学, 医科学研究所, 助手 (60240735) 正井久雄東京大学, 医科学研究所, 助教授 (40229349)
Keywords	増殖因子 / 染色体複製 / シグナル伝達 / サイトカイン / 増殖因子受容体 / 細胞周期 / 転写因子 / T細胞活性化
Research Abstract	1 1)GM-CSFレセプター(GMR)β鎖は、GM-CSFによってリン酸化される。2)GMRβ鎖のチロシン残基のリン酸化はβ鎖とShcやPTP1Dの会合と、c-fos遺伝子の活性化に重要な役割を果す。3)JAK2は、膜貫通部分直下領域に依存するDNA複製、c-myc遺伝子活性化と、よりC末端側領域に依存するc-fos遺伝子活性化の両者のシグナル伝達経路に必須な役割を果す。 2 ヒトNF-ATのアミノ酸配列に対応する3種のヒトcDNA(NF-ATp,c,x)とマウスNF-ATx cDNAを単離した。NF-ATxは新規の分子である。NF-ATxとc-fos/junの再構成によりIL-2遺伝子の転写は活性化される。更にThiとThzサブセット間ではNF-kBのp50/p65と(p50)2およびJunの存在状態に差異があることから、両者では、転写因子NF-kBとNF-AT/AP-1の活性化に至るシグナル伝達系に差異があることが強く示唆された。 3 S期開始のマスタースイッチであると考えられている出芽酵母CDC7キナーゼのキナーゼ変異体を大量発現することにより、野性型出芽酵母の増殖は1CDNAで停止した。キナーゼ変異Cdc7はそのregulatory subunitであるDbf4を吸収することにより野性型Ccd7を不活化すると結論した。 4 我々が昨年度単離した、分裂酵母のCDC7ホモログと考えられるHsk1のキナーゼ変異体の発現により、cdc2(ts)、cdc18(ts)株のG1/S移行が観察された。また、Hsk1蛋白質はin vitroで自己リン酸化した。以上の結果から、Hsk1はCdc2、cdc18タンパク質と相互作用し、分裂酵母のG1/Sを制御すると結論した。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Kinoshita,T.et al.: "Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors." EMBO J.14. 266-275 (1995)
[Publications] Kinoshita,T.et al.: "Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells." Oncogene. 10. 2207-2212 (1995)
[Publications] Masuda,E.et al.: "NFATx:a functional member of the NFAT family that is predominantly expressed in the thymus" Mol,Cell,Biol.15. 2697-2706 (1995)
[Publications] Watanabe,S.et al.: "Involvement of the interleukin-2 receptory γ subunit in interleukin-4-dependent activation of mouse hamatopoietic cells and splenic B cells." Ear,J.Immunol.25. 126-131 (1995)
[Publications] Kosugi,H.et al.: "Structure of the gene encoding the α subunit of the human interleukin-3 receptor" Biochem,Biophys.Res.Commun.208. 360-367 (1995)
[Publications] Muto,A.et al.: "High affinity chimeric human granulocyte-macrophage colony-stimulating factor receptor carrying the ctyoplasmic domain of the β subunit but not the a subunit transduces growh promoting signals in Ba/F3 cells." Biochem,Biophys.Res.Commun.208. 368-375 (1995)
[Publications] Tsuruta,L,et al.: "cAMP inhibits expression of the IL-2 gene through the NF-AT site and transfection of NF-AT cDNAs abrogates the sensitivity to" J.Immunol.154. 5255-5264 (1995)
[Publications] Nishinakamura,R.et al.: "Mice deficient for the IL-3/GM-CSF/IL-5 receptor exhibit lung pathology and impaired immune response" Immunity. 2. 215-222 (1995)
[Publications] Watanabe,S.et al.: "Granulocyte-macrophage colony stimulation factor dependent replication of polyoma virus replicon in hematopoietic cells : Analyses of recrptor signals for replication and transcription" J,Biol.Chem.270. 9615-9621 (1995)
[Publications] Watanabe,S.et al.: "Characterization of cis-regulatory elements of the c-myc promoter responding to human GM-CSF or mouse IL-3 in mouse proB cell line BA/F3 cells expressing the human GM-CSF receptor." Mol,Biol.Cell.6. 627-636 (1995)
[Publications] Nishijima,I.et al.: "A human GM-CSF receptor expressed in transgenic mice stimulates proliferation and differentiation of hemopoietic progenitors to all Iineages in response to human GM-CSF" Mol,Biol.Cell.6. 497-508 (1995)
[Publications] Masai,H.& Arai,K.: "Dna-A dependent assembly of the ABC primosome at the A site,a single-stranded DNA hairpin containing a dnaA box" Eur.J.Biochem.230. 384-395 (1995)
[Publications] Lee,H.J.et al.: "Definition of cis-regulatory elements of the mouse interleukin-5 promoter : involvement of NF-AT related factors in interleukin-5 expression" J.Biol.Chem.270. 17541-17550 (1995)
[Publications] Masai,H.et al.: "Schizosaccharomyces pombe homologue of Saccharomyces cerevisiae CDC7,is requred for chromosomal replication" EMBO J,. 14. 5338-5345 (1995)
[Publications] Ito,T.et al.: "Granulocyte-macrophage colony-stimulating factor provokes different modes of signalling leading to ras activation and transcription of c-fos through tyrosine residues of the receptor β subunit" J.Biol.Chem.270. 9615-9621 (1995)

1995 Fiscal Year Annual Research Report

増殖因子レセプターによるシグナル伝達と複製開始の制御に関する共同研究

Principal Investigator

新井 賢一 東京大学, 医科学研究所, 教授 (00012782)

Research Products

[Publications] Kinoshita,T.et al.: "Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors." EMBO J.14. 266-275 (1995)

[Publications] Kinoshita,T.et al.: "Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells." Oncogene. 10. 2207-2212 (1995)

[Publications] Masuda,E.et al.: "NFATx:a functional member of the NFAT family that is predominantly expressed in the thymus" Mol,Cell,Biol.15. 2697-2706 (1995)

[Publications] Watanabe,S.et al.: "Involvement of the interleukin-2 receptory γ subunit in interleukin-4-dependent activation of mouse hamatopoietic cells and splenic B cells." Ear,J.Immunol.25. 126-131 (1995)

[Publications] Kosugi,H.et al.: "Structure of the gene encoding the α subunit of the human interleukin-3 receptor" Biochem,Biophys.Res.Commun.208. 360-367 (1995)

[Publications] Muto,A.et al.: "High affinity chimeric human granulocyte-macrophage colony-stimulating factor receptor carrying the ctyoplasmic domain of the β subunit but not the a subunit transduces growh promoting signals in Ba/F3 cells." Biochem,Biophys.Res.Commun.208. 368-375 (1995)

[Publications] Tsuruta,L,et al.: "cAMP inhibits expression of the IL-2 gene through the NF-AT site and transfection of NF-AT cDNAs abrogates the sensitivity to" J.Immunol.154. 5255-5264 (1995)

[Publications] Nishinakamura,R.et al.: "Mice deficient for the IL-3/GM-CSF/IL-5 receptor exhibit lung pathology and impaired immune response" Immunity. 2. 215-222 (1995)

[Publications] Watanabe,S.et al.: "Granulocyte-macrophage colony stimulation factor dependent replication of polyoma virus replicon in hematopoietic cells : Analyses of recrptor signals for replication and transcription" J,Biol.Chem.270. 9615-9621 (1995)

[Publications] Watanabe,S.et al.: "Characterization of cis-regulatory elements of the c-myc promoter responding to human GM-CSF or mouse IL-3 in mouse proB cell line BA/F3 cells expressing the human GM-CSF receptor." Mol,Biol.Cell.6. 627-636 (1995)

[Publications] Nishijima,I.et al.: "A human GM-CSF receptor expressed in transgenic mice stimulates proliferation and differentiation of hemopoietic progenitors to all Iineages in response to human GM-CSF" Mol,Biol.Cell.6. 497-508 (1995)

[Publications] Masai,H.& Arai,K.: "Dna-A dependent assembly of the ABC primosome at the A site,a single-stranded DNA hairpin containing a dnaA box" Eur.J.Biochem.230. 384-395 (1995)

[Publications] Lee,H.J.et al.: "Definition of cis-regulatory elements of the mouse interleukin-5 promoter : involvement of NF-AT related factors in interleukin-5 expression" J.Biol.Chem.270. 17541-17550 (1995)

[Publications] Masai,H.et al.: "Schizosaccharomyces pombe homologue of Saccharomyces cerevisiae CDC7,is requred for chromosomal replication" EMBO J,. 14. 5338-5345 (1995)

[Publications] Ito,T.et al.: "Granulocyte-macrophage colony-stimulating factor provokes different modes of signalling leading to ras activation and transcription of c-fos through tyrosine residues of the receptor β subunit" J.Biol.Chem.270. 9615-9621 (1995)

新井賢一東京大学, 医科学研究所, 教授 (00012782)