CaMK-II promotes focal adhesion turnover and cell motility by inducing tyrosine dephosphorylation of FAK and paxillin.
CaMK-II promotes focal adhesion turnover and cell motility by inducing tyrosine dephosphorylation of FAK and paxillin.
复制标题
CAMK-II通过诱导FAK和Paxillin的酪氨酸去磷酸化来促进局灶性粘附周转和细胞运动。
DOI：
10.1002/cm.20294
复制
发表时间：
2008-08
影响因子：
--
通讯作者：
Tombes, Robert M.
中科院分区：
文献类型：
--
作者：
Easley, Charles A.;Brown, Claire M.;Horwitz, Alan F.;Tombes, Robert M.
Ca2+的短暂升高先前已被证明通过未知的机制促进局灶性黏附分解和细胞运动。在这项研究中，有证据表明CaMK-II， Ca2+/钙调蛋白依赖性蛋白激酶，影响成纤维细胞粘附和运动性。TIRF显微镜显示在迁移细胞的细胞表面CaMK-II的动态种群。两种机制不同的膜渗透抑制剂（k -93和myr-AIP）抑制CaMK-II冻结板足动力学，加速在纤维连接蛋白上的扩散，扩大含paxillin的局灶粘连并阻断细胞运动。相比之下，在细胞表面没有发现组成活性CaMK-II，减少细胞附着，从局灶粘连中消除paxillin，降低FAK和paxillin的磷酸酪氨酸水平；所有这些事件都可以通过myr-AIP逆转。因此，CaMK-II抑制和本构激活分别通过局灶黏附的过度稳定或不稳定来阻断细胞运动。再加上瞬态Ca2+升高和动态CaMK-II群体的存在，这些发现提供了第一个直接证据，证明CaMK-II通过瞬时和局部刺激局灶黏附蛋白的酪氨酸去磷酸化来促进局灶黏附周转，从而促进细胞运动。细胞Motil。
Transient elevations in Ca2+ have previously been shown to promote focal adhesion disassembly and cell motility through an unknown mechanism. In this study, evidence is provided to show that CaMK-II, a Ca2+/calmodulin dependent protein kinase, influences fibroblast adhesion and motility. TIRF microscopy reveals a dynamic population of CaMK-II at the cell surface in migrating cells. Inhibition of CaMK-II with two mechanistically distinct, membrane permeant inhibitors (KN-93 and myr-AIP) freezes lamellipodial dynamics, accelerates spreading on fibronectin, enlarges paxillin-containing focal adhesions and blocks cell motility. In contrast, constitutively active CaMK-II is not found at the cell surface, reduces cell attachment, eliminates paxillin from focal adhesions and decreases the phospho-tyrosine levels of both FAK and paxillin; all of these events can be reversed with myr-AIP. Thus, both CaMK-II inhibition and constitutive activation block cell motility through over-stabilization or destabilization of focal adhesions, respectively. Coupled with the existence of transient Ca2+ elevations and a dynamic CaMK-II population, these findings provide the first direct evidence that CaMK-II enables cell motility by transiently and locally stimulating tyrosine dephosphorylation of focal adhesion proteins to promote focal adhesion turnover. Cell Motil.
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DOI：
10.1006/bbrc.1998.9592
发表时间：
1998-11-09
影响因子：
3.1
作者：
Bouvard, D;Block, MR
通讯作者：
Block, MR
影响因子：
4.8
作者：
Bouvard, D;Vignoud, L;Block, MR
通讯作者：
Block, MR
影响因子：
4.7
作者：
Johnson, LD;Willoughby, CA;Tombes, RM
通讯作者：
Tombes, RM
影响因子：
4
作者：
Kohn, AD;Moon, RT
通讯作者：
Moon, RT
影响因子：
15.9
作者：
Bilato, C;Curto, KA;Crow, MT
通讯作者：
Crow, MT