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The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1

Academic Article
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Overview

authors

  • Kadrmas, J. L.
  • Smith, M. A.
  • Clark, K. A.
  • Pronovost, S. M.
  • Muster, N.
  • Yates III, John
  • Beckerle, M. C.

publication date

  • December 2004

journal

  • Journal of Cell Biology  Journal

abstract

  • Cell adhesion and migration are dynamic processes requiring the coordinated action of multiple signaling pathways, but the mechanisms underlying signal integration have remained elusive. Drosophila embryonic dorsal closure (DC) requires both integrin function and c-Jun amino-terminal kinase (JNK) signaling for opposed epithelial sheets to migrate, meet, and suture. Here, we show that PINCH, a protein required for integrin-dependent cell adhesion and actin-membrane anchorage, is present at the leading edge of these migrating epithelia and is required for DC. By analysis of native protein complexes, we identify RSU-1, a regulator of Ras signaling in mammalian cells, as a novel PINCH binding partner that contributes to PINCH stability. Mutation of the gene encoding RSU-1 results in wing blistering in Drosophila, demonstrating its role in integrin-dependent cell adhesion. Genetic interaction analyses reveal that both PINCH and RSU-1 antagonize JNK signaling during DC. Our results suggest that PINCH and RSU-1 contribute to the integration of JNK and integrin functions during Drosophila development.

subject areas

  • Actins
  • Animals
  • Animals, Genetically Modified
  • Cell Adhesion
  • Cell Movement
  • DNA-Binding Proteins
  • Drosophila
  • Drosophila Proteins
  • Epithelial Cells
  • Epithelium
  • Integrins
  • JNK Mitogen-Activated Protein Kinases
  • Mutation
  • Signal Transduction
  • Transcription Factors
  • Wings, Animal
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Identity

PubMed Central ID

  • PMC2034365

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.200408090

PubMed ID

  • 15596544
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Additional Document Info

start page

  • 1019

end page

  • 1024

volume

  • 167

issue

  • 6

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