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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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A novel protein kinase D phosphorylation site in the tumor suppressor Rab interactor 1 is critical for coordination

Susanne Ziegler1, Tim Eiseler, Rolf-Peter Scholz

  • 1Institute of Cell Biology and Immunology, University of Stuttgart, 70569 Stuttgart, Germany Panatecs GmbH, 72070 Tübingen, Germany.

Molecular Biology of the Cell
|January 7, 2011
PubMed

Insights

Researchers identified a new signaling pathway involving Ras and Rab interactor 1 (RIN1) and Protein Kinase D (PKD). This pathway regulates cell migration by controlling Abl kinase activation through RIN1 phosphorylation.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • Ras and Rab interactor 1 (RIN1) is a multifunctional signal adapter protein.
  • RIN1 regulates epithelial cell migration and endocytosis via Rab5 and Abl kinase pathways.
  • Protein Kinase D (PKD) was previously shown to phosphorylate RIN1 in vitro.

Purpose of the Study:

  • To identify in vivo phosphorylation sites of RIN1 by PKD.
  • To elucidate the role of RIN1 phosphorylation in cell migration.
  • To characterize the novel PKD signaling pathway involving RIN1 and Abl kinases.

Main Methods:

  • Phospho-specific antibody generation and validation.
  • Mass spectrometry for site identification.
  • Cell migration assays.
  • Kinase activity assays.

Main Results:

  • Serine 292 of RIN1 was identified as a novel in vivo PKD phosphorylation site.
  • PKD-mediated phosphorylation at serine 292 regulates RIN1's inhibition of cell migration.
  • Phosphorylation at serine 292 modulates Abl kinase activation.
  • RIN1 phosphorylation at serine 351 in vivo occurs independently of PKD.

Conclusions:

  • A novel PKD signaling pathway through RIN1 and Abl kinases regulates actin remodeling and cell migration.
  • PKD-mediated phosphorylation of RIN1 at serine 292 is a key regulatory mechanism in cell migration.
  • This study reveals a new layer of complexity in RIN1-mediated signaling.

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