One Isoform of Arg/Abl2 Tyrosine Kinase Is Nuclear and the Other Seven Cytosolic Isoforms Differently Modulate Cell Morphology, Motility and the Cytoskeleton

Exp Cell Res. 2013 Aug 1;319(13):2091-2102. doi: 10.1016/j.yexcr.2013.05.012. Epub 2013 May 23.

Abstract

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.

Keywords: Abelson related gene; Arg; Cell morphology; Cell motility; Cytoskeleton; Isoforms; Non-receptor tyrosine kinase Arg; Subcellular distribution.

MeSH terms

  • Animals
  • COS Cells
  • Cell Movement / genetics*
  • Cell Nucleus / enzymology*
  • Cell Shape / genetics
  • Chlorocebus aethiops
  • Cytoskeleton / enzymology*
  • Cytoskeleton / genetics
  • Cytosol / enzymology*
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / physiology
  • Protein Transport / genetics
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Isoenzymes
  • ARG tyrosine kinase
  • Protein-Tyrosine Kinases