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1996 Fiscal Year Final Research Report Summary

Molecular basis of pathophysiological role of Syk in blood and immumecells

Research Project

Project/Area Number 07457043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKOBE UNIVERSITY

Principal Investigator

YAMAMURA Hirohei  Kobe University School of Medicine Professor, 医学部, 教授 (90030882)

Co-Investigator(Kenkyū-buntansha) SADA Kiyonao  School of Medicine, Kobe University Research Associate, 医学部, 助手 (10273765)
YANAGI Shigeru  School of Medicine, Kobe University Research Associate, 医学部, 助手 (60252003)
MINAMI Yasuhiro  School of Medicine, Kobe University Associate Professor, 医学部, 助教授 (70229772)
Project Period (FY) 1995 – 1996
Keywordsprotein-tyrosine kinase / Syk / CD45 / Lyn / Zap-70 / cortactin / oxidative stress / DT-40 cell
Research Abstract

A non-receptor type protein-kinase Syk is expressed in almost all the hematopoietic cells. In this project we tried to found out the physiological role of Syk in signal transduction and also pathophysiological role od Syk. We have obtained the following results.
1)Human leukemic cell line K562 is induced to differentiate into the megakaryocytic lineage by stimulation with TPA.We found that TPA stimulation increases tyrosine phosphorylation of 80-kDa protein at an early stage of megakaryocytic differentiation and that this 80-kDa protein is identical with cortactin.
2)The roles of Syk and Lyn in radiation-induced signal transduction and radiation-induced apoptosis, we have studied using Syk-and Lyn-DT-40 cells. Syk and Lyn are involved in radiation-induced signaling, but inactivation of syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis.
3)We studied the relationship between Syk activity and cAMP.cAMP-dependent protein kinase negatively regulates the activation of Sy … More k in fMLP-receptor signaling in polymorphonuclear neutrophils.
4)To explore the mechanisim by which the Syk participates in B cell antigen receptor signaling, we have studied the function of various Syk mutants in B cells made Syk deficient by homologous recombination knockout. We foynd that both SH2 domains are necessary for Syk binding to tyrosine-phosphorvlated
5)We have succeeded in making a CD45-deficient DT-40 cells. Using this cell lines we have found that the dephosphorylation of tyrosine residues at both autophosphorylation and negative regulatory sites is mediated by CD45 in vivo and that dephosphorylation of C-terminal tyrosine is a prerequisite for participation of Lyn in B cell receptor signaling.
6)Syk is rapidely activated in B cells after hydrogen peroxide treatment (oxidative stress) or increased extracellular NaCl concentration (osmotic stress) as well as in response to B cell receptor activation. We have found that both the calcium increase and Jun-amino-teminal kinase (JNK) activity induced by oxidative stress are partly dependent on syk, whereas those induced by osmotic stress are independent of Syk.
7)We have been searching the family of Syk/Zap-70 in brain and other tissues. We found novel kinases in brain and liver cells. Now we are purifying these kinases and cloning the cDNAs of these kinases. Less

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Asahi, M. et. al.: "Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling." Biophys. Biochem. Res. Commun.212(3). 887-893 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurosaki, T. et. al.: "Syk recruitment to Ig-a and its phosphorylation are essential for B cell antigen receptor signaling." J. Exp. Med.182. 1815-1823 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Qin, S. et. al.: "Cooperation of tyrosinekinases p72sky and p53/56lyn regulates calcium mobilization in chicken B cell oxidant stress signaling." Eur. J. Biochem.236(2). 443-449 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maruyama, S. et. al.: "Physical and functional association of cortactin with Syk in human leukemic cell line K562." J. Biol. Chem.271(12). 6631-6635 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanagi, S. et. al.: "CD45 Modulates phosphorylation of Both Autophosphorylation and Negative Regulatory Tyrosines of Lyn in B Cells." J. Biol. Chem.271(48). 30487-30492 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Qin, S. et. al.: "Syk-dependent and-independent Signaling Cascades in B Cells Elicited by Osmotic and Oxidative Stress." J. Biol. Chem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Minami, Y., nakagawa, Y., Kawahara, A., Miyazaki, T., Sada, K., Yamamura, H.and Taniguchi, T.: "Protein-tyrosine kinase Syk is associated with and activated by the IL-2 receptor : Possible link with the c-myc induction pathway." Immunity. 2. 89-100 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai, K., Takata, M., Yamamura, H.and Kurosaki, T.: "Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling." J.Blol. Chem.270(12). 6824-6829 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagi, S., Kurosaki, K.and Yamamura, H.: "The structure and function of p72syk function of p72syk expressed in hematopoietic cells" Cellular Signalling. 7(3). 185-193 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Qin, S., Inazu, T.and Yamamura, H.: "Activation adn tyrosine phosphorylation of p72syk as well as calcium mobilization after hydrogen peroxide stimulation in peripheral blood lymphocytes." Biochem. J.(1995)308(1). 347-352 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamura, H.: "Syk Spleen tyrosine kinase (vertebrates) The Protein Kinase Factsbookedited by G.Hardie and S.Hanks" Academic Press Limited. Vol.II. 109-111 (1995)

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  • [Publications] Hirasawa, N., Scharenberg, A., Yamamura, H., Beaven, .M.A.and Kinet, J.-P.: "A requirement for syk in the activation of the microtubule-associatedprotein kinase/phospholipase A2 pathway by FreR1 is not shared by a G protein-coupled receptor." J.Biol. Chem.270(18). 10960-10967 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki, Y., Satoh, K., Kuroda, K., Qi, R., Yatomi, Y., Yanagi, S., Sada, K., Yamamura, H,.Yanabu, M., Nomura, S., and Kume, S..: "Anti-CD9 monoclonal antibody activates p72syk in human platelets" J.Biol. Chem.270(25). 15119-15124 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda, H., Inazu, T., Nagai, K., Maruyama, S., Nakagawara, G., and Yamamura, H..: "Possible involvement of protein-tyrosine kinases kinases such as p72syk in the Disc-Sphere change response of porcine platelets." J.Biochem. 117(6). 1201-1208 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yang, C., Maruyama, S., Yanagi, S.Wang, X., Takata, M., Kurosaki, T.and Yamamura, H.: "Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis. sufficient to prevent radiation-induced apoptosis." J.Biochem. 118(1). 33-38 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Asahi, M., Tanaka, Y., Qin, S., Tsubokawa, M., Sada, K., Minami, Y.and Yamamura, H.: "Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling." Biophys. Biochem. Res. Commun.212(3). 887-893 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Scharenberg, A.M., Lin, S., Cuenod, B., Yamamura, H., and Kinet, J.-P.: "Reconstitution of interactions between tyrosine kinases and the high affinity lgE receptor which are controlled by receptor clustering." EMBO J.14(14). 3385-3394 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E., Takeuchi, F., Tanaka, Y.and Yamamura, H.: "Purification and phosphory-lation of Mr 25,000 protein, an effective phosphate aceptor for casein kinase II and protein kinase C,detected in the cytosolic fraction of Xenopus laevus oocytes." J.Biochem.118(2). 453-460 (1995)

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  • [Publications] Ichinohe, T., Takayama, H., Ezumi, Y., Yanagi, S., Yamamura, H., and Okuma, M.: "Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI." J.Biol. Chem.270(47). 28029-28036 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Zeng, H., Yoshida, T., Kurosaki, T., Yamamura, H., Oshima, A., Kitamura, D., Watanabe, T.and Morikawa, M.: "Phosphorylation of HSI,GAP-associated p190 and a novel GAP-associated p60 protein by cross-linking of FcyRIIIA" J.Biochem.118(6). 1166-1174 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurosaki, T,.Johnson, S.A., Sada, K., Yamamura, H.and Cambier, J.C.: "Syk recruitment to Ig-a and its phosphorylation are essential for B cell antigen receptor signaling." J.Exp. Med.182. 1815-1823 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maruyama, S., Kurosaki, T., Sada, K., Yamanashi, Y., Yamamoto, T., and Yamamura, H.: "Physical and functional association of cortactin with Syk in human leukemic cell line K562." J.Biol. Chem.271(12). 6631-6635 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, E., Kobayashi, N., Kubota, N., Tanaka, Y., and Yamamura.H..: "Phosphorylated Sites of Mr 25,000 Protein, a Putative Protein Phosphatase 2A Modulator, and Phosphorylation of the Synthetic Peptide Containing These Sites by Protein Kinase C." J.Biochem.119(4). 626-632 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Qin, S., Inazu, T., Takata, M., Kurosaki, T., Chen, H., Homma, Y., and Yamamura, H.: "Cooperation of tyrosinekinases p72 syk andp53/56 lyn regulates calcium mobilization in chicken B cell oxidant stress signaling." Eur. J.Biochem.236(2). 443-449 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minami, Y., Qin, S., Sada, K,.Oishi, I., and Yamamura, H.: "Role of protein-tyrosine kinases in stress signaling." J.Deuterium Sci.5(1). 11-14 (1996)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura, T., Koyama, M., Yaneyama, A., Higashihara, M., Kawakami, T., Yamamura, H., Sada, K., Okumura, k., and Kurokawa, K.: "Sigunal transduction through mk B-cell receptors expressed on pre-Bcells is different from that through B-cell receptors on mature B cells." Immunology. 88. 593-599 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagi, S., Sugawara, H., Kurosaki, M., Sada, H., Yamamura, H., and Kurosaki, T.: "CD45 Modulates phosphorylation of Both Autophosphorylation and Negative Regulatory Tyrosines of Lyn in B Cells." J.Biol. Chem.271(48). 30487-30492 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Qin, S., Minami, Y., Hibi, M., Kurosaki, T., and Yamamura, H.: "Syk-dependent and-independent Signaling Cascades in B Cells Elicited by Osmotic and Oxidative Stress." J.Biol. Chem.(in perss.).

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      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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