与酶基质相互作用选相结合的PhosY-secretome分析定义了活性c-Src驱动的细胞外信号传递
Sarah J Backe1, SarahBeth D Votra1, Matthew P Stokes2
1Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Cell reports
|May 27, 2023
概括
分泌的c-Src氨酸激酶 (c-Src) 有助于细胞外酸化. 用抗体准细胞外c-Src通过破坏酶基质复合体来抑制癌细胞的增殖.
科学领域:
- 蜂信号传输是如何进行的
- 癌症生物学 癌症生物学
- 蛋白质的生物化学 蛋白质的生物化学
背景情况:
- c-Src氨酸激酶是一种关键的细胞内信号分子和癌症治疗点.
- 细胞外作用和c-Src的分泌机制在很大程度上是未知的.
- 了解细胞外c-Src功能对于开发新型癌症疗法至关重要.
研究的目的:
- 为了阐明c-Src分泌的机制.
- 为了确定c-Src.的细胞外基质和相互作用部位.
- 研究细胞外c-Src在癌症进展中的作用,并确定治疗点.
主要方法:
- 域删除突变发生,以确定c-Src分泌所必需的区域.
- 有限的蛋白质溶解合质谱测量用于识别c-Src基质和相互作用点.
- 进行比较性蛋白质组分析以表征分泌体.
- 使用SH3向抗体抑制细胞外c-Src.
主要成果:
- c-Src的N-近端区域对于其分泌至关重要.
- 组织金属蛋白酶2抑制剂 (TIMP2) 是c-Src的细胞外基质.
- c-Src的SH3域和TIMP2的P31VHP34基因对它们的相互作用至关重要.
- 细胞外c-Src产生富含PxxP动机的分泌体,促进癌症.
- 抗体介导的细胞外c-Src抑制会破坏复合体并减少癌细胞的增殖.
结论:
- c-Src在细胞外酸化和分泌体生成中起着重要作用.
- 细胞外c-Src会影响细胞间的通信,特别是在具有高c-Src表达的癌症中.
- 针对细胞外c-Src及其相互作用,为癌症治疗提供了一个有前途的治疗策略.
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