Signal transduction of Proteoglycan-type protein tyrosine phosphatase, PTPS.

蛋白聚糖型蛋白酪氨酸磷酸酶（PTPS）的信号转导。

• 批准号: 13680699
• 负责人: MAEDA Nobuaki
• 金额: $ 2.3万
• 依托单位: Tokyo Metropolitan Organization for Medical Research (2002)Okazaki National Research Institutes (2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680699/
• 关键词: PTPζ; proteoglycan; pleiotrophin; midkine; Purkinje cell; chondroitin sulfate; コンドロイチン硫酸; 樹状突起; プレイオトロフィン(PTN); ミッドカイン(MK); プルキンエ細胞; PTPS; GIT; 脳; ヘパリン結合性成長因子

PTPζ is a receptor-type protein tyrosine phosphatase, which is abundantly expressed in the developing brain as a chondroitin sulfate proteoglycan. PTPζ binds with pleiotrophin and midkine with high affinity. The chondroitin sulfate portion of PTPζ plays essential roles in the binding to these growth factors. Removal of chondroitin sulfate chains from PTPζ by chondroitinase ABC digestion resulted in the marked decrease of the binding affinity to pleiotrophin and midkine and the loss of signal transduction. The fine structure of chondroitin sulfate chains of PTPζ regulates its binding to these growth factors. Chondroitin sulfate chains of PIPζ contain about 1% D-unit, which seems to be the essential structure for the high affinity binding to pleiotrophin and midkine.Immunohistochemical analysis of PTPζ, pleiotrophin and chondroitin sulfate D-unit demonstrated that the expression of these molecules are highly correlated with the dendrite formation of cerebellar Purkinje cells. So, we examined the roles of PTPζ in the morphogenesis of Purkinje cells using organotypic slice culture system of rat cerebellum. Abnormal Purkinje cells with disoriented and/or multiple primary dendrites markedly increased by the additions of (1)polyclonal antibodies against PTPζ, (2) sodium vanadate, a protein tyrosine phosphatase inhibitor, (3) chondroitinase ABC, (4)chondroitin sulfate D, and (5) pleiotrophin. These results suggest that pleiotrophin-PTPζ signaling regulates the morphogenesis of Purkinje cell dendrites.We also tried to identify the substrate molecules of PTPζ using the yeast substrate-trapping system. This method is based on the yeast two-hybrid system, with two modufucations : conditional expression of v-src to tyrosine phosphorylate the prey proteins and screening by using a substrate-trap mutant of PTPζ. By this system, we identified GIT1/Cat-1 as a substrate.

Ptpζ IS A Receptor-Type Protein Tyrosine Phosphatase, Which Is Abundantly Expressed in The Developing Brain as a INDS WITH PLEITROPHIN AND MIDKINE WITH HIGH HIGH AFFINITY. The ChoneDroitin SULFATE PTPPζ Plays Essential RoleS in the Removal of CHAINS from PTPζ by ChoneDroitinase ABC Digested in The在硫酸盐链中，在硫酸盐链的硫酸盐链1％D-UNIT中明显降低了与多叶蛋白的结合亲和力。 Midkine。对PTPζ，硫酸硫酸盐D- just的硫酸盐的表达表明，这些分子的表达高度与小脑Purkinje细胞的树突高度相关。针对PTPζ，（2）d和（5）多叶素。调节：V-Src对酪氨酸疗法的有条件表达祈祷蛋白质，并通过使用PTPζ的底物 - 陷阱突变体筛选。

项目成果

Tanaka, M., Maeda, N.et al.: "A chondroitin sulfate proteoglycan PTPζ/RPTP β regulates the morphogenesis of purkinje cell dendrites in the developing cerebellum"Journal of Neuroscience. (in press). (2003)

Tanaka, M., Maeda, N. 等人：“硫酸软骨素蛋白聚糖 PTP z/RPTP β 调节发育中小脑中浦肯野细胞树突的形态发生”《神经科学杂志》（2003 年出版）。

前田信明: "PTPζのシグナル伝達機構と脳の形態形成"細胞工学. 20. 1107-1113 (2001)

Nobuaki Maeda：“PTPζ信号转导机制和大脑形态发生”《细胞工程》20。1107-1113（2001）。

Kawachi, H. et al.: "Identification of GIT1/Cat-1 as substrate molecule of protein tyrosine phosphates ζ/β by the yeast substrate-trapping system"Proc. Natl. Acad. Sci. USA. 98. 6593-6598 (2001)

Kawachi, H. 等人：“通过酵母底物捕获系统鉴定 GIT1/Cat-1 作为蛋白质酪氨酸磷酸盐的底物分子”，Proc. Acad. 98. 6593-6598。 2001）

Kawachi, H., Fujikawa, A., Maeda, N., Noda, M.: "Identification of GITl/Cat 1 as a substrate molecule of protein tyrosid phosrphatase ζ/β by yeast substrate-trapping system"Proc Natl, Acad. Sci. USA. 98(12). 6593-6598 (2001)

Kawachi，H.，Fujikawa，A.，Maeda，N.，Noda，M.：“通过酵母底物捕获系统鉴定 GIT1/Cat 1 作为蛋白酪氨酸磷酸酶 z/β 的底物分子”Proc Natl，Acad。科学。98(12)。

Qi, M.et al.: "Haptotactic migration induced by midkine: Involvement of protein-tyrosine phosphatase, mitogen-activated protein kinase and phosphatidylinositol 3-kinase"J. Biol. Chem.. 276. 15868-15875 (2001)

Qi, M.等：“中期因子诱导的触触迁移：蛋白酪氨酸磷酸酶、丝裂原激活蛋白激酶和磷脂酰肌醇 3-激酶的参与”J.