One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton (Retracted Article)
One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton (Retracted Article)
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DOI：
10.1016/j.yexcr.2013.05.012
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发表时间：
2013-08-01
影响因子：
3.7
通讯作者：
Perego, Roberto A.
中科院分区：
文献类型：
--
作者：
Bianchi, Cristina;Torsello, Barbara;Perego, Roberto A.
非受体酪氨酸激酶Abelson相关基因(Arg/Abl2)通过调节细胞骨架来调节细胞的迁移和形态发生。Arg通过激活RhoA抑制剂p190RhoGAP来减弱应力纤维的形成和收缩能力，并通过CrkII磷酸化来调节焦点黏附动力学，从而促进基于肌动蛋白的细胞突起和扩散，并抑制细胞迁移。八种具有不同N-末端和C-末端的全长Arg异构体在人类细胞中内源性表达。本文将8种亚克隆到pFLAG-CMV2载体中的8种Arg亚型分别导入COS-7细胞，研究其在细胞形态、迁移和细胞骨架调控中的亚细胞分布及作用。转染的1BSCTS Arg异构体在细胞核内呈核内分布，并使CrkII磷酸化，而其他异构体则在细胞质中检测到。1BLCTL、1BSCTL、1ASCTS亚型能显著减少应力纤维，诱导细胞收缩和丝状突起，并显著增加p190RhoGAP的磷酸化。相反，1ALCTL、1ALCTS、1ASCTL和1BLCTS亚型并不显著减少应力纤维和诱导形成收缩尾状突起。1BLCTL和1ALCTL亚型对细胞迁移和灶性黏附有不同的影响。这些数据可能为研究细胞侵袭机制开辟新的视角。(C)2013 Elsevier Inc.保留所有权利。
The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. Arg promotes actin-based cell protrusions and spreading, and inhibits cell migration by attenuating stress fiber formation and contractility via activation of the RhoA inhibitor, p190RhoGAP, and by regulating focal adhesion dynamics also via CrkII phosphorylation. Eight full-length Arg isoforms with different N- and C-termini are endogenously expressed in human cells. In this paper, the eight Arg isoforms, subcloned in the pFLAG-CMV2 vector, were transfected in COS-7 cells in order to study their subcellular distribution and role in cell morphology, migration and cytoskeletal modulation. The transfected 1BSCTS Arg isoform has a nuclear distribution and phosphorylates CrkII in the nucleus, whilst the other isoforms are detected in the cytoplasm. The 1BLCTL, 1BSCTL, 1ASCTS isoforms were able to significantly decrease stress fibers, induce cell shrinkage and filopodia-like protrusions with a significant increase in p190RhoGAP phosphorylation. In contrast, 1ALCTL, 1ALCTS, 1ASCTL and 1BLCTS isoforms do not significantly decrease stress fibers and induce the formation of retraction tail-like protrusions. The 1BLCTL and 1ALCTL isoforms have different effects on cell migration and focal adhesions. All these data may open new perspectives to study the mechanisms of cell invasiveness. (C) 2013 Elsevier Inc. All rights reserved.