c端Src激酶(埋头)和CSK-homologous激酶(分)——内生Src-family的负调控蛋白激酶。
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Chong YP, Mulhern TD,程恩华HC
c端Src激酶(埋头)和CSK-homologous激酶(分)——内生Src-family的负调控蛋白激酶。
生长因子。2005年9月,23 (3):233 - 44。
- PubMed ID
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16243715 (在PubMed]
- 文摘
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c端Src激酶(埋头)和CSK-homologous激酶(分)是内源性Src-family蛋白酪氨酸激酶抑制剂(SFKs)。自本构激活SFKs有助于癌症的形成和发展,为了防止过度激活SFKs,他们的活动在正常细胞保存在埋头基准面,嗯。埋头,嗯灭活SFKs专门磷酸化的酪氨酸达成共识(称为Y (T)) c终端附近。磷酸化后,phospho-Y (T)参与分子内相互作用,锁SFK分子的活性构象。SFKs固定在质膜,而埋头和分本地化主要在胞质。抑制SFKs,埋头,又需要把等离子体膜。招聘埋头和分质膜是由绑定的SH2, SH3和/或特定的跨膜蛋白激酶域,g和适配器蛋白质位于质膜。埋头,膜招聘经常伴随激活。埋头,又采用两种类型的直接交互,SFKs实现高效Y (T)磷酸化:(i)短程相互作用涉及到绑定的活性埋头往嘴里特定场所附近残留Y (T),(2)远程非交互涉及到绑定的SFKs图案位于活跃的站点的远侧地埋头,嗯。埋头和SFKs瞬态之间的交互。 Unlike CSK, CHK binds tightly to SFKs to form stable protein complexes. The binding is non-catalytic as it is independent of Y(T). More importantly, the tight binding alone is sufficient to completely inhibit SFKs. This non-catalytic inhibitory binding represents a novel mechanism employed by CHK to inhibit SFKs. Given that SFKs are implicated in cancer development, compounds mimicking the non-catalytic inhibitory mechanism of CHK are potential anti-cancer therapeutics.