Physiology and Developmental Biology, Brigham Young University, 574 WIDB, Provo, UT 84602, USA.
Biochem Biophys Res Commun. 2011 Oct 14;414(1):215-9. doi: 10.1016/j.bbrc.2011.09.059. Epub 2011 Sep 17.
Vasodilator-stimulated phosphoprotein (VASP) is an actin regulatory protein that functions in adhesion and migration. In epithelial cells, VASP participates in cell-cell adhesion. At the molecular level, VASP drives actin bundling and polymerization. VASP activity is primarily regulated by phosphorylation. Three physiologically relevant phosphorylation sites significantly reduce actin regulatory activity and are targeted by several kinases, most notable Abl and protein kinases A and G (PKA and PKG). AMP-dependent kinase (AMPK) is best characterized as a cellular sensor of ATP depletion, but also alters actin dynamics in epithelial cells and participates in cell polarity pathways downstream of LKB1. While little is known about how AMPK direct changes in actin dynamics, AMPK has been shown to phosphorylate VASP at one of these three well-characterized PKA/PKG phosphorylation sites. Here we show that phosphorylation of VASP by AMPK occurs at a novel site, serine 322, and that phosphorylation at this site alters actin filament binding. We also show that inhibition of AMPK activity results in the accumulation of VASP at cell-cell adhesions and a concomitant increase in cell-cell adhesion.
血管扩张刺激磷蛋白（VASP）是一种肌动蛋白调节蛋白，在黏附和迁移中发挥作用。在上皮细胞中，VASP 参与细胞-细胞黏附。在分子水平上，VASP 驱动肌动蛋白成束和聚合。VASP 的活性主要受磷酸化调节。三个与生理相关的磷酸化位点显著降低肌动蛋白调节活性，并且是几种激酶的靶标，其中最显著的是 Abl 和蛋白激酶 A 和 G（PKA 和 PKG）。AMP 依赖的激酶（AMPK）最被认为是细胞内 ATP 耗竭的传感器，但也改变上皮细胞中的肌动蛋白动力学，并参与 LKB1 下游的细胞极性途径。虽然人们对 AMPK 如何直接改变肌动蛋白动力学知之甚少，但 AMPK 已被证明可在上调这三个 PKA/PKG 磷酸化位点之一磷酸化 VASP。在这里，我们显示 AMPK 对 VASP 的磷酸化发生在一个新的丝氨酸 322 位点，并且该位点的磷酸化改变了肌动蛋白丝的结合。我们还表明，抑制 AMPK 活性会导致 VASP 在细胞-细胞黏附处积累，并伴随着细胞-细胞黏附的增加。
