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1992 Fiscal Year Final Research Report Summary

Protein-tyrosine phosphorylation and its biological significance

Research Project

Project/Area Number 02304034
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionFukui Medical School

Principal Investigator

YAMAMURA Hirohei  Fukui Medical School Professor, 医学部, 教授 (90030882)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Masashi  The Institute of Medical Science, The University of Tokyo Professor, 医科研, 教授 (40134621)
EBINA Yousuke  The Institute for Enzyme Research, The University of Tokushima Professor, 酵素研, 教授 (00112227)
TAKEDA Masao  Hiroshima University School of Medicine Professor, 医学部, 教授 (40030853)
KASUGA Masato  Kobe University School of Medicine Professor, 医学部, 教授 (50161047)
NAKAGAWA Hachirou  Osaka University Medical School Professor, 蛋白研, 教授 (20029937)
Project Period (FY) 1990 – 1992
KeywordsP72^<syk> / P60^<src> / EGF-receptor tyrosine kinase / CSK / cDNA cloning / Insulin-receptor kinase / PI-3 kinase / Protein-tyrosine phosphatase
Research Abstract

During 3 years we studied about physiological significance of protein-tyrosine phosphorylation. Some of the representative results are itemized. 1. Insulin causes the association of PI 3-kinase with IRS-1 (insulin receptor substrate 1) via phosphorylated YMXM motifs of IRS-1 and SH2 domain of p85. (Kasuga) 2. Study of abnormal messenger ribonucleic acid (mRNA) transcribed from a mutant insulin receptor gene in a patient with type A insulin resistance. (Yoshida) 3. Purification and characterization of a rat liver protein-tyrosine phosphatase with sequence similarity to src-homology region 2. (Hiraga) 4. Study of signal transduction system for growth factor receptors associated with tyrosine kinase: Epidermal growth factor receptor signalling and its regulation. (Iwashita) 5. Purification and characterization of a rat liver membrane tyrosine-protein kinase, the possible protooncogene c-yes product,p60^<c-yes>. (Takeda) 6. Src-like protein-tyrosine kinase Lyn is functionally associated with membrane-bound immunoglobulin M and seems likely to participate in B-cell antigen receptor-mediating signaling. (Yamamoto) 7. Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negatively regulatory site of p60^<c-src>.(Nakagawa) 8. The alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase is phosphorylated at tyrosines 368, 580 and 607 by the insulin receptor. (Ebina) 9. Study of involvement of the membrane cytoskeletal protein and the src gene product in growth cone adhesion and movement. (Sobue) 10. Cloning of a new number of nonreceptor type protein-tyrosine kinase having an apparent molecular mass of 72 kDa. (Yamamura)

  • Research Products

    (78 results)

All Other

All Publications (78 results)

  • [Publications] Jun Sukegawa: "Monoclonal antibodies to the amino-terminal unique seique sequence of the c-yes-1 gene product as specific probes of expression." Oncogene. 5. 611-614 (1990)

    • Description
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  • [Publications] Kazushi Inoue: "Specific expression of human c-fgr in monocytes and large granular lymphocytes,effectors of natural immunity." Mol.Cell.Biol.10. 1789-1792 (1990)

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  • [Publications] Takeshi Yagi: "Homologous recombination at c-fyn locus of mouse embryonic stem cells with diphtheria toxin A fragment gene in negative selection." Proc.Natl.Acad.Sci.USA. 87. 9918-9922 (1990)

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  • [Publications] Koko Katagiri: "Expression of src family genes during monocytic differentiation of HL 60 cells." J.Immunol.146. 701-709 (1990)

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  • [Publications] Hashimoto,E.: "Comparison of substrate recognition by protein kinase C(type III)between rat liver cytosolic particulate fractions." Int.J.Biochem.22(4). 405-410 (1990)

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  • [Publications] Kobayashi,T.: "purification and characterization of a cytosolic protein-tyrosine kinase from porcine spleen." Eur.J.Biochem.188(3). 535-540 (1990)

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  • [Publications] Asahi,M.: "Diverse effects of poly-basic amino acids,heparin and ionic strength on the phosphorylation of various substrates by cytosolic protein-tyrosine kinase from porcine spleen." Int.J.Biochem. 22(6). 635-640 (1990)

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  • [Publications] Inazu,T.: "Protein-tyrosphorylation and aggregation of intact human platelets by vanadate with H_2O_2" Biochem.Biophys.Res.Commun.170(1). 259-263 (1990)

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  • [Publications] Hashimoto,E.: "Mechanism of proteolytic activation of rat liver protein kinase C generating Ca^<2+>-phospholipid-independent form with apparent molecular mass of 80,000." Int.J.Biochem.22(8). 865-871 (1990)

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  • [Publications] Hashimoto,E.: "Protease-activated form of protein kinase C with Mr 80,000 generated from rat liver plasma membrane by trypsin-like protease." Biochem.Int.21(5). 949-957 (1990)

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  • [Publications] Sobue,K.: "Involvement of the membrane cytoskeletal proteinsand the src gene product in growth cone adhesion and movement." Neurosci.Res.Suppl.13. 80-91 (1990)

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  • [Publications] Yamamoto,R.: "Defect in tyrosine kinase activity of the insulin receptor from a patient with insulin resistance and acanthosis nigricans." J.Clin.Endocrinol.Metab.70. 869-878 (1990)

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  • [Publications] Tobe,K.: "Immunological detection of phosphotyrosine-containing proteins in rat liver after insulin injection." Diabetes.39. 528-533 (1990)

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  • [Publications] Shiba,T.: "Concanvalin A-induced receptor aggregation stimulates the tyrosine kinase activity of the insulin receptor in intact cells." Biochem.J.267. 787-794 (1990)

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  • [Publications] Yamamoto,R.: "Phosphorylation state and bioligical function of a mutant human insulin receptor Va1996." J.Biol.Chem.265. 14777-14783 (1990)

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  • [Publications] Shimada,F.: "Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene." Lancet. 335. 1179-1181 (1990)

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  • [Publications] Iwashita,S.: "cAMP-mediated modulation of signal transduction of epidermal growth factor (EGF) receptor systems in human epidermoid carcinoma A431 cells. Depression of EGF-denendent diacylglycerol producti and EGF receptor phosphorylation." J.Biol.Chem.265. 10702-10708 (1990)

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  • [Publications] Mitsui,K.: "Examination of the role of serine phosphoylation in phospholipase C-g and its related p47 in cAMP-mediated depression of epidermal growth factor receptor signal transduction." FEBS Letters. 268. 157-160 (1990)

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  • [Publications] Nada,S.: "Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60^<c-src>." Nature. 351. 69-72 (1991)

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  • [Publications] Okada,M.: "CSK:a protein-tyrosine kinase involved in regulation of src family kinases." J.Biol.Chem.266. 24249-24252 (1991)

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  • [Publications] Yuji Yamanashi: "Associations of B cell antigen receptor and protein-tyrosine kinase p561yn." Science. 251. 192-194 (1991)

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  • [Publications] Kazuyoshi Azuma: "Purification and characterization of a rat liver membrane tyrosine kinase,the possible protooncogene c-yes product,p60^<c-yes>." J.Biol.Chem.266. 4831-4839 (1991)

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  • [Publications] Yumiko Matsrzawa: "Characterization of the promoter region of the yes-protooncogene." Oncogene. 6. 1561-1568 (1991)

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  • [Publications] Sachiko Tsukita: "The c-yes and lyn tyrosine kinases are specifically enriched in cell-cell adherence junctions." J.Cell Biol.113. 867-879 (1991)

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  • [Publications] Yuji Yamanashi: "Differential responses of p56^<lyn> and p531^<yn>,products of alternatively spliced lyn mRNA,upon stimulation of B cell antigen receptor." Cell Regulation. 2. 979-987 (1991)

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  • [Publications] Masato Okada: "CSK:A protein-tyrosine kinase invoved in regulation of src-family kinases." J.Biol.Chem.266. 24249-24252 (1991)

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  • [Publications] KAzuyoshi Azuma: "Purification and characterization of a rat liver membrane tyrosine-protein kinase,the possible protooncogene c-yes product,p60c-yes." J.Biol.Chem.266. 4831-4839 (1991)

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  • [Publications] Hashimoto,E.: "Studies on protein kinase C tightly-bound to rat liver plasma membrane and its protease-activated form." Int.J.Biochem.23(4). 395-403 (1991)

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  • [Publications] Hashimoto,E.: "Protease-activated protein kinase C in rat liver." Int.J.Biochem.23(5/6). 507-512 (1991)

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  • [Publications] Shimomura,R.: "Possible endogenous substrate proteins for cytosolic protein-tyrosine kinase from porcine spleen." Int.J.Biochem.23(7/8). 727-731 (1991)

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  • [Publications] Taniguchi,T.: "Molecular cloning of a porcine gene syk that encodes a 72kDa protein-tyrosine kinase showing high susceptibility to proteolysis." J.Biol.Chem.266(19). 15790-15796 (1991)

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  • [Publications] Yamada,T.: "The lectin wheat germ agglutinin stimulates a protein-tyrosine kinase activity of p72^<syk> in porcine splenocytes." Biochem.Biophys.Res.Commun.180(3). 1325-1329 (1991)

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  • [Publications] Sakai,K.: "Identification of the phosphorylation sites of H2B histone by a catalytic fragment of p72^<syk> from porcine spleen." FEBS Lett.294(1,2). 104-108 (1991)

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  • [Publications] Hayashi,K.: "Structural and functional relationships brtween h-and l-caldesmon." J.Biol.Chem.266. 355-361 (1991)

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  • [Publications] Tanaka,T.: "Ca^<2+>-dependent regulation of the spectrin/actin interaction by calmodulin and protein4.1." J.Biol.Chem.266. 1134-1140 (1991)

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  • [Publications] Sobue,K.: "Caldesmon,a novel regulatory protein in smooth muscle and nonmuscle actomyosin systems." J.Biol.Chem.266. 12115-12118 (1991)

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  • [Publications] Izumi,T.: "Insulin and platelet-derived growth factor stimulate phosphorylation of the c-raf product at serine and threonine residues in intact cells." J.Biol.Chem.266. 7933-7939 (1991)

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  • [Publications] Tobe,K.: "Insulin and 12-o-teradecanoylphobol 13-acetate (TPA) activation of two immunologically distinct MBP/MAP2 kinases via de novo phosphorylation of threonine and tyrosine residues." J.Biol.Chem.266. 24793-24803 (1991)

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  • [Publications] Eiich Araki: "A Cluster of four Spl Binding Sites Required for Efficient Expression of the Human Insulin Receptor Gene." J.Biol.Chem.266. 3944-3948 (1991)

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  • [Publications] Hideki Hayashi: "Phosphorylation in vitro of the 85kDa subunit of phosphatidylinositol 3-kinase and its possible activation by insulin receptor tyrosine kinase." Biochem.J.280. 769-775 (1991)

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  • [Publications] Suzuki,Y.: "Defects in insulin binding and receptor kinase in cells from a woman with type A insulin resistance and from her family." Diabetologia. 34. 86-92 (1991)

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  • [Publications] Tokuyama,Y.: "Hypersecretion of islet amyloid polypeptide from pancreatic islets of ventromedial hypothalamic-lesioned rats and obese Zucker rats." Endocrinology. 128. 2739-2744 (1991)

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  • [Publications] Yamori,T.: "Insulin-like growth factor I rapidly induces tyrosine phosphorylation of a Mr 150,000 and a Mr 160,000 protein in highly metastatic mouse colon carcinama 26 NL-17 cells." Cancer Research. 51. 5859-5865 (1991)

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  • [Publications] Akira Hiraga: "Rat liver protein-tyrosine phosphatases:purification and characterization of two forms." Adv.Protein Phosphatases. 6. 251-264 (1991)

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  • [Publications] Sabe,H.: "Molecular cloning and expression of chicken C-terminal Src kinase:lack of stable association with c-Src protein." Proc.Natl.Acad.Sci.USA. 89. 2190-2194 (1992)

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  • [Publications] Sabe,H.: "Activation of c-Src in cells bearing v-Crk and its suppression by Csk." Mol.Cell.Biol.12. 4706-4713 (1992)

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  • [Publications] Junichiro Muzuguchi: "Tyrosine protein kinase is involved in anti-IgM-mediated signalling in Ball 7 B lymphoma cells." J.Immunol.148. 689-694 (1992)

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  • [Publications] Yuji Yamanashi: "Activation of Src-like protein-tyrosine kinase Lyn and Lyn associated PI-3 kinase upon B cell antigen receptor-mediated signaling." Proc.Natl.Acad.Sci.USA. 89. 1118-1122 (1992)

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  • [Publications] Koko Katagiri: "Modulation of monocytic differenatiation of HL 60 cells by inhibitors of protein-tyrosine kinases." Cell Immunol.140. 282-294 (1992)

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  • [Publications] Hisashi Umemori: "Specific expression of antigen receptor-associated tyrosine kinases,Fyn and Lyn,in the central nernous system." Mol.Cell Biol.12. 3784-3795 (1992)

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  • [Publications] Fumiaki Uchiumi: "Characterization of the promoter region of the src-family gene lyn and its trans-activation by HTL V-I encoded p40tax." Mol.Cell.Biol.12. 3784-3795 (1992)

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  • [Publications] Takahiro Miyauchi: "Purification and characterization of a possible protooncogene fyn product,p59^<fyn>,from a rat brain particulate fraction." J.Biochem.112. 729-732 (1992)

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  • [Publications] Takeuchi,F.: "Phosphorylation of histone H2A by protein kinase C and identification of the phosphorylation site." J.Biochem.111(6). 788-792 (1992)

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  • [Publications] Ohta,S.: "Protein-tyrosine phosphorylations induced by concanavalin A and N-formyl-methionyl-phenylalanine in human neutrophils." Eur.J.Biochem.206(3). 895-900 (1992)

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  • [Publications] Ohta,S.: "Protein-tyrosine kinase p72^<syk> is activated by wheat germ agglutinin in platelets." Biochem.Biophys.Res.Commun.185(3). 1128-1132 (1992)

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  • [Publications] Asahi,M.: "Thrombin-induced human platelet aggregation is inhibited by protein-tyrosine kinase inhibitors,ST638 and genistein." FEBS Lett.309(1). 10-14 (1992)

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  • [Publications] Takeuchi,N.: "Inhibotory effect of mitoxantrone on activity of protein kinase C and Growth of HL60 cells." J.Biochem.112(6). 762-767 (1992)

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  • [Publications] Hayashi,K.: "Genomic structure of human caldesmon gene." Proc.Natl.Acad.Sci.USA. 89. 12116-12122 (1992)

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  • [Publications] Yonezawa,K.: "In vitro association of phosphatidylinositol 3-kinase activity with the activated insulin receptor tyrosine kinase." J.Biol.Chem.267. 440-446 (1992)

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  • [Publications] Chatami,Y.: "Mitogen-induced tyrosine-phosphorylated 41-and 43-kDa proteins are family members of extracellular signal-regulated kinases/microtubule-associated protein 2 kinases." J.Biol.Chem.267. 9911-9916 (1992)

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  • [Publications] Ando,A.: "Enhanced insulin-induced mitogenesis and mitogen-activated protein kinase activities in mutant insulin receptors with substitution of two COOH-terminal tyrosine autophosphorylation sites by phenylalanine." J.Biol.Chem.267. 12788-12796 (1992)

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  • [Publications] Yonezawa,K.: "Insulin-dependent formation of a complex containing 85-kDa subunit of PI3-kinase and tyrosine-phosphorylated IRS-1." J.Biol.Chem.267. 25958-25966 (1992)

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  • [Publications] Takashi Murakami: "Idenification of Two Enhancer Elements in the Gene Encoding the Type 1 Glucose Transporter from the Mouse Which Are Responsive to Serum,Growth Factor,and Oncogenes." J.Biol.Chem.267. 9300-9306 (1992)

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  • [Publications] Hideki Hayashi: "Insulin Treatment Stimulates the Tyrosine Phosphorylation of the α-Type 85-kDa subunit of Phosphatidylinositol 3-Kinase in Vivo." J.Biol.Chem.267. 22575-22580 (1992)

    • Description
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  • [Publications] Shimada,F.: "Abnormal messenger ribonucleic acid(mRNA) transcribed from a mutant insulin receptor gene in a patient with type A insulin resistance." Diabetologia. 35. 639-644 (1992)

    • Description
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  • [Publications] Makino,H.: "Insulin receptor gene mutation:a molecular genetical and functional analysis." Cellular Signaling. 4. 351-363 (1992)

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  • [Publications] Iwashita,S.: "Signal transduction system for growth factor receptors associated with tyrosine kinase activity:Epidermal growth factor receptor signalling and its regulation." Cellular Signalling,. 4. 123-132 (1992)

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  • [Publications] Nakamura,T.: "Isolation and characterization of activin receptor from mouse embryonal carcinoma cells.Identification of its serine/threonine/tyrosine protein kinase activity." J.Biol.Chem.267. 18924-18928 (1992)

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  • [Publications] Akira Hiraga: "Purification and characterization of a rat liver protein-tyrosine phosphatase with sequence similarity to src-homology region 2." Eur.J.Biochem.209(1). 195-206 (1992)

    • Description
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  • [Publications] Taniguchi,T.: "Protein-tyrosine kinase p72^<syk> is activated by thrombin in platelets." J.Biol.Chem.268(4). 2277-2279 (1993)

    • Description
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  • [Publications] Akira Hiraga: "Identification of a rat liver protein-tyrosine phosphatase similar to human placental PTPase-lB using quantitatively phosphorylated protein substrates." J.Biochem.113(2). 180-188 (1993)

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  • [Publications] Marius Sudol: "Novel Yes-related kinase,Yrk,is expressed at elevated levels in neural and hematopoietic tissues." Oncogene.

    • Description
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  • [Publications] Yuji Yamanashi: "Identificarion of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B cell antigen receptor-mediated signaling." Proc.Natl.Acad.Sci.USA.

    • Description
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  • [Publications] Takahiro Miyauchi: "Purification and characteriation of the possible protooncogene fyn product,p59fyn,from rat brain particulate fraction." J.Biochem.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koko Katagiri: "Tyrosine phosphorylation of tubulins during monocytic differentiation of HL-60 cells." J.Immunol.

    • Description
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  • [Publications] Tadashi Yamamoto: "Association of Src-family kinase Lyn with B-cell antigen receptor." Immu.Rev.

    • Description
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  • [Publications] Tanaka,J.: "Morphological and Biochemical analyses of contractile proteins (actin,myosin,caldesmon and tropomyosin) in normal and transformed cells." J.Cell Sci.

    • Description
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  • [Publications] Hideki Hayashi: "The a-Type 85-kDa Subunit of Phosphatidylinositol 3-Kinase Phosphorylated at Tyrosines368,580,and 607 by the Insulin Receptor." J.Biol.Chem.

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Published: 1994-03-24  

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