1998 Fiscal Year Annual Research Report

神経系における新規Sykファミリーチロシンキナーゼの同定および機能解析

Research Project

Project/Area Number	09470043
Research Institution	KOBE UNIVERSITY
Principal Investigator	山村博平神戸大学, 医学部, 教授 (90030882)
Co-Investigator(Kenkyū-buntansha)	高野智子神戸大学, 医学部, 助手 (30226807) 柳茂神戸大学, 医学部, 助手 (60252003)
Keywords	チロシンキナーゼ / Syk / チロシン燐酸化 / 肝臓細胞 / 神経系 / 血管内皮細胞 / 血管 / 平滑筋細胞
Research Abstract	1. ラット肝臓の免疫組織染色の結果、Sykは脳および肝実質の細胞質画分に検出され、高感度RT-PCR Northern解析の結果、ラット肝臓においてSykは脾臓の約3-5%程度の発現が確かめられた。2. ラット肝細胞由来の2種類の細胞株でSykが発現しており、酸化ストレスなどの刺激によりSykの急速な活性化および自己リン酸化が認められた。 3. 胚性癌細胞由来の細胞株p19を神経細胞へと分化誘導させることにより、Sykのチロシンリン酸化が誘導され、神経細胞におけるSykの機能が示唆された。 4. 血管内皮細胞および血管平滑筋細胞においてもSykの発現が確かめられ、アンギオテンシンIIや様々な生理的リガンド刺激によりSykの急速な活性化が認められた。この結果はSykノックアウトが出血で出産後すぐに死亡することと密接に関係していると考えられる。 5. 腎臓の繊維芽細胞にも高いSykの発現が観察された。これらの結果より、血球系特異的シグナル分子と考えられたSykは、非血球系組織に広汎に分布していることが明らかとなった。今後、さらにSykの役割を神経系と脈管系に注目し、Sykのノックアウトマウスを中心に解析していきたい。また血球系細胞における各種ストレスによるSykの活性化についても興味ある知見を得たが、神経系におけるSykとの関係を調べて行く上に貴重な結果であると考えている。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Qin,S.: "Differential regulation of oxidative and osmotic stress-induced Syk activation by both autophosphorylation and SH2 domains." Biochemistry. 37. 5481-5486 (1998)
[Publications] Oishi,I.: "A novel drosophila nuclear protein serine/threonin kinase expressed in the germ line during its establishment." Mech.Dev.71. 49-63 (1998)
[Publications] Yoneya,H.: "Antibodies directed against ZAP-70 cross react with a 66 kDa tyrosine kinase in the rat brain." Biochem.Biophys.Res.Commun.245(1). 140-143 (1998)
[Publications] Rezaul,K.: "Involvement of reactive oxygen intermediates in lectin-induced protein-tyrosine phosphorylation of Syk in THP-1 cells." Biochem.Biophys.Res.Commun.246(3). 863-867 (1998)
[Publications] Liu,Z-J.: "A critical role for cyclin C in promotion of the hematopoietic cell cycle by cooperation with c-Myc." Molecular and Cellular Biology. 18(6). 3445-3454 (1998)
[Publications] Qin,S.: "A deficiency in Syk enhances ceramide-induced apoptosis in DT40 lymphoma B cells." FEBS Lett.427. 139-143 (1998)
[Publications] Tohyama,Y.: "Outside-in signaling of soluble and solid-phase fibrinogen through integrin α IIB β3 is different and cooperative with cach pther in a megakaryoblastic leukemia cell,CMK." Blood. 92(4). 1277-1288 (1998)
[Publications] Liu,Z-J.: "Functional cooperation of cyclin C and c-Mycin mediating homotypic cell,adhesion via very late antigen-4 activation and vascular cell adhesion,molccule-1 induction." Blood. 92(12). 1-13 (1998)
[Publications] Hitomi,T.: "Cross-iinking of the B cell receptor induces activation of phospholipase D through Syk,Btk and phospholipase C-γ2." FEBS Lett.'(in press). (1999)
[Publications] Sada,K.: "Effect of lectins on protein kinase activity. In Lectin Methods and Protocols." Edited by J.M.Rhodes and J.D.Milton. Humana Press Inc., 423-432 (1998)
[Publications] Minami,Y.: "Roles of Syk protein tyrosine kinase in stress-inkuced signaling in B cells. Redox Regulation of Cell Signaling and its Clinical Applications." Marcel DekkerInc.NY,USA.(in press), (1998)

1998 Fiscal Year Annual Research Report

神経系における新規Sykファミリーチロシンキナーゼの同定および機能解析

Principal Investigator

山村 博平 神戸大学, 医学部, 教授 (90030882)

Research Products

[Publications] Qin,S.: "Differential regulation of oxidative and osmotic stress-induced Syk activation by both autophosphorylation and SH2 domains." Biochemistry. 37. 5481-5486 (1998)

[Publications] Oishi,I.: "A novel drosophila nuclear protein serine/threonin kinase expressed in the germ line during its establishment." Mech.Dev.71. 49-63 (1998)

[Publications] Yoneya,H.: "Antibodies directed against ZAP-70 cross react with a 66 kDa tyrosine kinase in the rat brain." Biochem.Biophys.Res.Commun.245(1). 140-143 (1998)

[Publications] Rezaul,K.: "Involvement of reactive oxygen intermediates in lectin-induced protein-tyrosine phosphorylation of Syk in THP-1 cells." Biochem.Biophys.Res.Commun.246(3). 863-867 (1998)

[Publications] Liu,Z-J.: "A critical role for cyclin C in promotion of the hematopoietic cell cycle by cooperation with c-Myc." Molecular and Cellular Biology. 18(6). 3445-3454 (1998)

[Publications] Qin,S.: "A deficiency in Syk enhances ceramide-induced apoptosis in DT40 lymphoma B cells." FEBS Lett.427. 139-143 (1998)

[Publications] Tohyama,Y.: "Outside-in signaling of soluble and solid-phase fibrinogen through integrin α IIB β3 is different and cooperative with cach pther in a megakaryoblastic leukemia cell,CMK." Blood. 92(4). 1277-1288 (1998)

[Publications] Liu,Z-J.: "Functional cooperation of cyclin C and c-Mycin mediating homotypic cell,adhesion via very late antigen-4 activation and vascular cell adhesion,molccule-1 induction." Blood. 92(12). 1-13 (1998)

[Publications] Hitomi,T.: "Cross-iinking of the B cell receptor induces activation of phospholipase D through Syk,Btk and phospholipase C-γ2." FEBS Lett.'(in press). (1999)

[Publications] Sada,K.: "Effect of lectins on protein kinase activity. In Lectin Methods and Protocols." Edited by J.M.Rhodes and J.D.Milton. Humana Press Inc., 423-432 (1998)

[Publications] Minami,Y.: "Roles of Syk protein tyrosine kinase in stress-inkuced signaling in B cells. Redox Regulation of Cell Signaling and its Clinical Applications." Marcel DekkerInc.NY,USA.(in press), (1998)

山村博平神戸大学, 医学部, 教授 (90030882)