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1994 Fiscal Year Final Research Report Summary

Action of novel non-receptor type protein-tyrosine kinase, p72^<syk>in immune cells.

Research Project

Project/Area Number 05670117
Research Category

Grant-in-Aid for General Scientific Research (C)

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

Principal Investigator

YANAGI Shigeru  Fukui Medical School, Research Associate, 医学部, 助手 (60252003)

Co-Investigator(Kenkyū-buntansha) YAMAMURA Hirohei  Fukui Medical School Professor, 医学部, 教授 (90030882)
Project Period (FY) 1993 – 1994
KeywordsSyk / protein-tyrosine kinase / B cell / Gene targeting / Lyn / Calcium mobilization / platelets / Translocation
Research Abstract

We have reported a porcine gene sky encoding a non-receptor type 72-kDa PTK (p72^<syk>) which has a distinct structural character, that is the presence of the second src homology region 2 (SH2) instead of SH3, from other members of this group of PTK.Our efforts have in large part focused on the relationship between Syk in the context of surface receptor-initiated signal transduction in B cell and platelet because of their abundant localization.
Stimulation of B lymphocytes through their antigen receptor (BCR) result in rapid increases and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. The BCR associates with two classes of tyrosine kinase : Src family kinase and Sky kinase. To dissect the functional roles of these two types of kinase in BCR signaling, Syk-deficient cell and Lyn-deficient cell lines were established. Syk-deficient cells abolished the tyrosine phosphorylation phospholipase C (PLC) -gamma, resulting in no inositol, 1,4,5-tris … More phosphate (IP3) generation, as well as calcium moblization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayd and slow calcium moblization, despite the normal kinetics of IP3 turnover. These results demonstrated that Syk mediates IP3 generation, whereas Lyn regulates calcium mobization through a process independent of IP3 generation.
Activation of Syk in platelets is not restricted to thrombin stimulation. Platelet activating factor, thromboxane A2, wheat germ agglutinin, and collagen also activate Syk. These findings imply that Syk may be one of the key molecules through which various receptor signaling acts. Tyrosine phosphorylation of p125^<FAK> is followed by Syk activation upon integrin receptor stimulation, suggesting that phosphorylation of p125^<FAK> may be mediated by Syk. Reinforcing this idea, the physical association of Syk family PTKs with Src family PTKs or FAK family protein is observed. Furthermore, stimulation of platelets by thrombin induces the rapid translocation of Syk from the cytosolic fraction to the membrane and cytoskeletal fraction. This recruitment of Syk to membrane and cytoskeletal fraction may contribute to the thrombininduced activation of Syk. Less

  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Taniguchi,T.: "Protein-tyrosine kinase p72syk is activated by thrombin and is negatively regulated through Ca_<2+> Mobilization in platelets." J.Biol.Chem.268. 2277-2279 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimomura,R.: "Phosphorylation sites of myelin basic protein by a catalytic fragment of non-receptor type protein-tyrosine kinase p72syk and comparison with those by insulin receptor kinase." Biochem.Biophys.Res.Commun.192. 252-260 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada,T.: "Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM." Eur.J.Biochem.213. 455-459 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeuchi,F.: "The lectin concanavalin a stimulates a protein-tyrosine kinase p72syk in peripheral blood lymphocytes." Biochem.Biophys.Res.Commun.194. 91-96 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeuchi,N.: "Possible role of Na+influx in phorbol ester-induced down regulation of protein kinase C in HL60 cells." FEBS Lett.328. 280-284 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asahi,M.: "Activation of protein-tyrosine kinase p72syk with Concanavalin A in polymorphonuclear neutrophils." J.Biol.Chem.268. 23334-23338 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda,H.: "Protein-tyrosine kinase p72syk is activated by thromboxane A2 mimetic U44069 in platelets." Biochem.Biophys.Res.Commun.197. 62-67 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takata,M.: "Tyrosine kinase Lyn and Syk regulate the B cell receptor-coupled Ca2+ mobilization through the distinct pathway" EMBOJ.13. 1341-1349 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sada,K.: "Activation of p72 syk by thrombin in a cell-free system." Biochem.Biophys.Res.Commun.200. 1-7 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yang,C.: "Purification and characterization of a protein-tyrosine Kinase p72syk from Porcine spleen" Eur.J.Biochem.221. 973-978 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurosaki,T.: "Syk activation by the src-family tyrosine kinase in the B cell receptor signaling" J.Exp.Med.179. 1725-1729 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsubokawa,M.: "CPTK71,a cytosolic protein-tyrosine kinase proviously purified from bovine platelets,is identical with p72syk." Biochem.Biophys.Res.Commun.200. 1592-1597 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Qin,S.: "Interleukin 2 Mediates p72syk activation in peripheral blood lymphocytes.21GC13:FEBS Lett." 345. 233-236 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanagi,S.: "Translocation,Activation,and Association with P13 Kinase of p72syk.are early Events during platelet Activation." Eur.J.Biochem.224. 329-333 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujii,C.: "Protein-tyrosine kinase p72syk.is activated by collagen in platelets." Eur.J.Biochem.226. 243-248 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang,X.: "Intracellular Calcium Dependent Activation of p72syk in Platelets" J.Biochem.116. 858-861 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagai,K.: "p72syk is activated by vanadate plus H202 in porcine platelets and phosphorylates GTP ase activating protein on tyrosine residue(s)" J.Biochem.116. 1176-1181 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tohyama,Y.: "Translocation of p72syk to the Cytoskeleton in Thrombin-Stimulated Platelets." J.Biol.Chem.269. 32796-32799 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Rezaul,K.: "Protein-tyrosine kinase p72syk is activatedby platelet activationg factor in platelets." Thrombosis and Haemostasis.72. 937-941 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Minami,Y.: "Protein Tyrosine Kinase Syk Is Associated with and Activated by The IL-2 Receptor,Possible Link with The c-myc Induction Pathway." Immunity. ((in press))

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagai,K.: "Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaing." J.Biol.Chem.((in press.))

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Qin,S.: "Activation and tyrosine phosphorylation of p72^<syk> as well as calcium mobilization after hydrogen peroxide stimulation in peripheral blood Iymphocytes" Biochem.J.((in press.))

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 箸本英吉: "実験医学" 羊土社, 6 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 谷口隆信: "実験医学" 羊土社, 6 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 箸本英吉: "現代化学" 東京化学同人, 7 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山村博平: "レセプター基礎と臨床" 朝倉書店, 6 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 稲津哲也: "実験医学" 羊土社, 2 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柳茂: "生化学" 日本生化学会, 11 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamura,H.: "The protein kinase Factsbook" Academic Press Limited, ((in press))

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniguchi, T., Kitagawa, H., Yasue, S., Yanagi, S., Sakai, K., Asahi, M., Ohta, S., Takeuchi, F., Nakamura, S.and Yamamura, H.: "Protein-tyrosine kinase p72syk is activated by thrombin and is negatively regulated through Ca2+ Mobilization in platelets." J.Biol.Chem. 268(4). 2277-2279 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimomura, R., Sakai, K., Tanaka, Y., Yonezawa, K., Hashimoto, E., Kasuga, M.and Yamamura, H.: "Phosphorylation sites of myelin basic protein by a catalytic fragment of non-receptor type protein-tyrosine kinase p72syk and comparison with those by insulin receptor kinase." Biochem.Biophys.Res.Commun.192(1). 252-260 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, T., Taniguchi, T., Yang, C.Yasue, S.Saito, H.and Yamamura, H.: "Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM." Eur.J : Biochem.213. 455-459 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeuchi, F., Taniguchi, T., Maeda, H., Fujii, C., Takeuchi, N.and Yamamura, H.: "The lectin concanavalin a stimulates a protein-tyrosine kinase p72syk in peripheral blood lymphocytes." Biochem.Biophys.Res.Commun.194(1). 91-96 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeuchi, N., Hashimoto, E., Nakamura, T., Takeuchi, F., Sada, K.and Yamamura, H.: "Possible role of Na+ influx in phorbol ester-induced down regulation of protein kinase C in HL60 cells." FEBS Lett.328. 280-284 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asahi, M., Taniguchi, T., Hashimoto, E., Inazu, T., Maeda, H.and Yamamura, H.: "Activation of protein-tyrosine kinase p72syk with Concanavalin A in polymorphonuclear neutrophils." J.Biol.Chem.268(31). 23334-23338 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda, H., Taniguchi, T., Inazu, T., Yang, C.Nakagawara and Yamamura, H.: "Protein-tyrosine kinase p72syk is activated by thromboxane A2 mimetic U44069 in platelets." Biochem.Biophys.Res.Commun.197(1). 62-67 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takata, M., Sabe, H., Hata, A., Inazu, T., Homma, Y., Nukada, T., Yamamura, H.and Kurosaki, T.: "Tyrosine kinase Lyn and Syk regulate the B cell receptor-coupled Ca2+ mobilization through the distinct pathway." EMBOJ.13(6). 1341-1349 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sada, K., Yanagi, S.and Yamamura, H.: "Activation of p72syk by thrombin in a cell-free system." Biochem.Biophys.Res.Commun.200(1). 1-7 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yang, C., Yanagi, S., Wang, X., Taniguchi, T., Sakai, K.and yamamura, H.: "Purification and characterization of a protein-tyrosine kinase p72syk from spleen" Eur.J.Biochem.221. 973-978 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurosaki, T., Takata, M., Yamanashi, Y., Inazu, T., Taniguchi, T., Yamamoto, T.and Yamamura, H.: "Syk activation by the src-family tyrosine kinase in the B cell receptor signaling" J.Exp.Med.179. 1725-1729 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsubokawa, M., Yanagi, S., Sada, K., Nakamura, S., Saito, H.and Yamamura, H.: "CPTK71, a cytosolic protein-tyrosine kinase previously purified from bovine platelets, is identical with p72syk." Biochem.Biophys.Res.Commun.200(3). 1592-1597 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Qin, S., Inazu, T., yang, C., sada, K., Taniguchi, T.and Yamamura, H: "Interleukin 2 Mediates p72syk activation in peripheral blood lymphocytes." FEBS Lett.345. 233-236 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagi, S., Sada, K., Toyama, Y., Tsubokawa, M., Nagai, K., Yoneawa, K.and Yamamura, H.: "Translocation, Activation, and Association with P13 Kinase of p72syk.are early Events during Platelet Activation." Eur.J.Biochem.224. 329-333 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujii, C., Yanagi, S., Sada, K., Nagai, K., Taniguchi, T.and Yamamura, H.: "Protein-tyrosine kinase p72syk.is activated by collagen in platelets" Eur.J.Biochem.226. 243-248 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wang, X., Sada, K., Yanagi, S., Yang, C., Rezaul, K.and Yamamura, H.: "Intracellular Calcium Dependent Activation of p72syk in Platelets" J.Biochem.116. 858-861 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai, K., Inazu, T.and Yamamura, H.: "p72syk is activated by vanadate plus H202 in porcine platelets and phosphorylates GTPase activating protein on tyrosine residue(s)." J.Biochem.116. 1176-1181 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tohyama, Y., Yanagi, S., Sada, K.and Yamamura, H.: "Translocation of p72syk to the Cytoskeleton in Thrombin-Stimulated Platelets." J.Biol.Chem.269. 32796-32799 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Rezaul, K., Yanagi, S., Sada, K., Taniguchi, T.and Yamamura, H.: "Protein-tyrosine kinase p72syk is activatedby platelet activating factor in platelets." Thrombosis and Haemostasis.72(6). 937-941 (1994)

    • Description
      「研究成果報告書概要(欧文)」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. (in press).

    • Description
      「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 signaing." J.Biol.Chem. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Qin, S., Inazu, T.and Yamamura, H.: "Activation and tyrosine phosphorylation of p72^<syk> as well as calcium mobilization after hydrogen peroxide stimulation in peripheral blood lymphocytes" Biochem.J.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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