Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell invasion
Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell invasion
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DOI：
10.1128/mcb.01832-07
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发表时间：
2008-06-01
影响因子：
5.3
通讯作者：
Alahari, Suresh K.
中科院分区：
文献类型：
--
作者：
Ding, Yuemin;Milosavljevic, Tanja;Alahari, Suresh K.
Nischarin是一种通过抑制p21激活激酶（PAK）来调节细胞迁移的新型蛋白质。LIM激酶（LIMK）是PAK的下游效应子，并且已知其在细胞侵袭中起重要作用。在这里，我们表明，nischarin也与LIMK抑制LIMK激活，cofilin磷酸化，和LIMK介导的乳腺癌细胞的侵袭，表明nischarin调节细胞侵袭的负调制LIMK/cofilin途径。Nischarin的氨基末端与LIMK的PDZ和激酶结构域结合。尽管LIMK的激活增强了与Nischarin的相互作用，但只有LIMK的苏氨酸508的磷酸化对于相互作用是至关重要的。通过RNA干扰抑制内源性Nischarin表达刺激乳腺癌细胞侵袭。此外，nischarin小干扰RNA（siRNA）增强cofilin磷酸化。此外，敲低nischarin显示分支的突起肌动蛋白结构。总的来说，这些数据表明，nischarin siRNA可以增强随机迁移，导致刺激入侵。
Nischarin is a novel protein that regulates cell migration by inhibiting p21-activated kinase (PAK). LIM kinase (LIMK) is a downstream effector of PAK, and it is known to play an important role in cell invasion. Here we show that nischarin also associates with LIMK to inhibit LIMK activation, cofilin phosphorylation, and LIMK-mediated invasion of breast cancer cells, suggesting that nischarin regulates cell invasion by negative modulation of the LIMK/cofilin pathway. The amino terminus of nischarin binds to the PDZ and kinase domains of LIMK. Although LIMK activation enhances the interaction with nischarin, only phosphorylation of threonine 508 of LIMK is crucial for the interaction. Inhibition of endogenous nischarin expression by RNA interference stimulates breast cancer cell invasion. Also, nischarin small interfering RNA (siRNA) enhances cofilin phosphorylation. In addition, knock-down of nischarin showed branched projection actin structures. Collectively these data indicate that nischarin siRNA may enhance random migration, resulting in stimulation of invasion.