1996 Fiscal Year Final Research Report Summary
Molecular basis of pathophysiological role of Syk in blood and immumecells
| Project/Area Number |
07457043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | KOBE UNIVERSITY |
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Principal Investigator |
YAMAMURA Hirohei Kobe University School of Medicine Professor, 医学部, 教授 (90030882)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Keywords | protein-tyrosine kinase / Syk / CD45 / Lyn / Zap-70 / cortactin / oxidative stress / DT-40 cell |
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| 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
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[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
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[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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[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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[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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[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)
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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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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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