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通过桩蛋白、细胞外信号调节激酶和肌球蛋白轻链激酶的黏着斑激酶-原癌基因酪氨酸蛋白激酶信号传导调节黏附解离。

FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly.

作者信息

Webb Donna J, Donais Karen, Whitmore Leanna A, Thomas Sheila M, Turner Christopher E, Parsons J Thomas, Horwitz Alan F

机构信息

Department of Cell Biology, UVA School of Medicine, P.O. Box 800732, Charlottesville, Virginia 22908-0732, USA.

出版信息

Nat Cell Biol. 2004 Feb;6(2):154-61. doi: 10.1038/ncb1094. Epub 2004 Jan 25.

Abstract

Cell migration is a complex, highly regulated process that involves the continuous formation and disassembly of adhesions (adhesion turnover). Adhesion formation takes place at the leading edge of protrusions, whereas disassembly occurs both at the cell rear and at the base of protrusions. Despite the importance of these processes in migration, the mechanisms that regulate adhesion formation and disassembly remain largely unknown. Here we develop quantitative assays to measure the rate of incorporation of molecules into adhesions and the departure of these proteins from adhesions. Using these assays, we show that kinases and adaptor molecules, including focal adhesion kinase (FAK), Src, p130CAS, paxillin, extracellular signal-regulated kinase (ERK) and myosin light-chain kinase (MLCK) are critical for adhesion turnover at the cell front, a process central to migration.

摘要

细胞迁移是一个复杂的、高度调控的过程,涉及黏附的持续形成与解体(黏附周转)。黏附形成发生在突起的前沿,而解体则发生在细胞尾部和突起的基部。尽管这些过程在迁移中很重要,但调节黏附形成和解体的机制仍然很大程度上未知。在这里,我们开发了定量分析方法来测量分子掺入黏附的速率以及这些蛋白质从黏附中脱离的速率。使用这些分析方法,我们表明激酶和衔接分子,包括黏着斑激酶(FAK)、Src、p130CAS、桩蛋白、细胞外信号调节激酶(ERK)和肌球蛋白轻链激酶(MLCK)对于细胞前端的黏附周转至关重要,而黏附周转是迁移的核心过程。

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