Cyclic mechanical stretch decreases cell migration by inhibiting phosphatidylinositol 3-kinase- and focal adhesion kinase-mediated JNK1 activation

Leena P. Desai, Steven R. White, Christopher Waters

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Epithelial cell migration during wound healing requires coordinated signaling pathways that direct polarization of the leading and trailing ends of the cells, cytoskeletal organization, and remodeling of focal adhesions. These inherently mechanical processes are disrupted by cyclic stretch (CS), but the specific signaling molecules involved in this disruption are not well understood. In this study, we demonstrate that inhibition of phosphatidylinositol 3-kinase (PI3K) or expression of a dominant-negative form of PI3K caused inhibition of airway epithelial cell wound closure. CS caused a sustained decrease in activation of PI3K and inhibited wound healing. Expression of constitutively active PI3K stimulated translocation of Tiam1 to the membrane, increased Rac1 activity, and increased wound healing of airway epithelial cells. Increased Rac1 activity resulted in increased phosphorylation of JNK1. PI3K activation was not regulated by association with focal adhesion kinase. Restoration of efficient cell migration during CS required coexpression of constitutively active PI3K, focal adhesion kinase, and JIP3.

Original languageEnglish (US)
Pages (from-to)4511-4519
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number7
DOIs
StatePublished - Feb 12 2010

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Phosphatidylinositol 3-Kinase
Focal Adhesion Protein-Tyrosine Kinases
Cell Movement
Chemical activation
Wound Healing
Epithelial Cells
Mechanical Phenomena
Phosphorylation
Focal Adhesions
Restoration
Adhesion
Association reactions
Polarization
Membranes
Molecules
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Cyclic mechanical stretch decreases cell migration by inhibiting phosphatidylinositol 3-kinase- and focal adhesion kinase-mediated JNK1 activation. / Desai, Leena P.; White, Steven R.; Waters, Christopher.

In: Journal of Biological Chemistry, Vol. 285, No. 7, 12.02.2010, p. 4511-4519.

Research output: Contribution to journalArticle

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