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RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration

Hailiang Hu1, Joanne M Bliss, Ying Wang

  • 1David Geffen School of Medicine, Department of Biological Chemistry, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90095, USA.

Current Biology : CB
|May 12, 2005
PubMed
Abstract

Insights

RIN1 activates ABL tyrosine kinases, influencing cell adhesion and migration. This discovery reveals a new signaling pathway for actin remodeling in response to environmental cues.

Area of Science:

  • Cell Biology
  • Molecular Signaling

Background:

  • ABL tyrosine kinases regulate actin remodeling, impacting cell adhesion, migration, and cell-cell contact.
  • Upstream mechanisms controlling ABL protein activation remain largely uncharacterized.

Purpose of the Study:

  • To investigate the upstream regulators of ABL tyrosine kinase activation.
  • To elucidate the role of RIN1 in ABL kinase signaling and its impact on cellular processes.

Main Methods:

  • Investigated RIN1-ABL2 interactions using biochemical assays.
  • Assessed ABL kinase activity upon RIN1 binding.
  • Utilized cell-based assays with fibroblasts and mammary epithelial cells (MECs).
  • Employed gene knockdown techniques and knockout mouse models (Rin1-/-).

Main Results:

  • RIN1 directly binds to ABL SH3 and SH2 domains, activating ABL2 catalytic activity.
  • RIN1 promotes membrane spike formation, similar to ABL overexpression.
  • Activated RAS forms a complex with RIN1 and ABL2, enhancing RIN1's ABL2 activation function.
  • RIN1 deficiency in MECs leads to accelerated cell adhesion and increased motility.
  • RIN1 knockdown in epithelial cells inhibits CRKL phosphorylation, indicating its role in motility regulation.

Conclusions:

  • RIN1 acts as a direct activator of ABL tyrosine kinases in cellular and in vitro systems.
  • A novel signaling pathway involving RIN1 mediates actin remodeling crucial for epithelial cell adhesion and migration in response to environmental stimuli.

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