Differential interaction of CrkII adaptor protein with plateletderived growth factor alpha-and beta-receptors is determined bu its internal tyrosine phosphorylation

CrkII 衔接蛋白与血小板源性生长因子 α 和 β 受体的差异相互作用是通过其内部酪氨酸磷酸化来确定的

• 批准号: 11838002
• 负责人: MORI Seijiro
• 金额: $ 2.05万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11838002/
• 关键词: platelet-derived growth factor receptor; Crk; tyrosine phosphorylation; 動脈硬化; 血小板由来増殖因子

CrkII is an intracellular adaptor protein involved in signal transduction by various growth factors. Activation of PDGF alpha-receptor resulted in its association with CrkII in vivo. In contrast, binding of CrkII to the PDGF beta-receptor was negligible, despite its becoming prominently phosphorylated. Bacterially expressed GST-CrkII SH2 domain specifically bound to Tyr-762 and Tyr-771 in the activated PDGF alpha-and beta-receptors, respectively. GST fusion protein of full-length CrkII also bound to the activated PDGF beta-receptor. However, tyrosine phosphorylation of GST-CrkII diminished its binding to the beta-receptor. CrkI, a truncated version of CrkII lacking the phosphorylatable tyrosine residue, could bind to both PDGF alpha-and beta-receptors in vivo. In conclusion, tyrosine phosphorylation of CrkII negatively affects its binding to the PDGF receptors. The differential binding of CrkII to the PDGF alpha-and beta-receptors may be a rationale for functional diversity between the two receptors.

CrkII是一种细胞内衔接蛋白，参与各种生长因子的信号转导。PDGF α受体的激活导致其与体内CrkII的结合。相反，CrkII与PDGF β-受体的结合可以忽略不计，尽管其变得显著磷酸化。细菌表达的GST-CrkII SH 2结构域分别与活化的PDGF α-和β-受体中的Tyr-762和Tyr-771特异性结合。全长CrkII的GST融合蛋白也与活化的PDGF β受体结合。然而，GST-CrkII的酪氨酸磷酸化减弱了其与β受体的结合。CrkI是缺少磷酸化酪氨酸残基的CrkII的截短版本，可以在体内与PDGF α和β受体结合。总之，CrkII的酪氨酸磷酸化对其与PDGF受体的结合产生负面影响。CrkII与PDGF α-和β-受体的差异结合可能是两种受体之间功能多样性的基本原理。

项目成果

Matsumoto, T et al: "Differential interaction of CrkII adaptor protein with platelet-derived growth factor alpha-and beta-receptor is determined by its internal tyrosine phosphorylation."Biochemical and biophysical Research communications. 270. 28-33 (200

Matsumoto, T 等人：“CrkII 衔接蛋白与血小板衍生生长因子 α 和 β 受体的不同相互作用是由其内部酪氨酸磷酸化决定的。”生物化学和生物物理研究通讯。

Minoru Takemoto: "Enhanced expression of osteopontin by high glucose in cultured rat aortic smooth muscle cells"Biochem. Biophys. Res. Commun.. 258. 722-726 (1999)

Minoru Takemoto：“培养的大鼠主动脉平滑肌细胞中高葡萄糖增强骨桥蛋白的表达”Biochem。

Taro M.Itsumoto, et al: "Differential interaction of Crkll adapter protein with platelet-derived growth factor alpha- and beta-receptors is determined by its internal tyrosine phosphorylation"Biochemical and Biophysical Research Communications. 270. 28-33

Taro M.Itsumoto 等人：“CrkII 衔接蛋白与血小板衍生生长因子 α 和 β 受体的差异相互作用是由其内部酪氨酸磷酸化决定的”《生物化学和生物物理研究通讯》。

Taro Matsumoto,Seijiro Mori, et al: "Differential interaction of Crkll adapter protein with platelet-derived growth factor alpha-and beta-receptors is determined by its internal tyrosine phosphorylation"Biochemical and Biophysical Research Communications.

Taro Matsumoto、Seijiro Mori 等人：“Crkll 接头蛋白与血小板衍生生长因子 α 和 β 受体的差异相互作用是由其内部酪氨酸磷酸化决定的”生物化学和生物物理研究通讯。

Taro Matsumoto: "Platelet-derived growth factor activatees p38 mitogen-activated protein kinase through a Rasdependent pathway that is important for actin reorganization and cell migration"J. Biol. Chem.. 274. 13954-13960 (1999)

Taro Matsumoto：“血小板源性生长因子通过 Ras 依赖性途径激活 p38 丝裂原激活蛋白激酶，这对于肌动蛋白重组和细胞迁移非常重要”J.