Requirement of phosphatidylinositol-3 kinase for epithelial cell migration activated by human macrophage stimulating

M H Wang1, F A Montero-Julian, I Dauny

  • 1Laboratory of Immunobiology, National Cancer Institute and Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702, USA.

Oncogene
|November 21, 1996
PubMed

Insights

Macrophage stimulating protein (MSP) activates the RON receptor, triggering epithelial cell migration. This process requires phosphatidylinositol-3 (PI-3) kinase activation, suggesting roles in tissue repair and metastasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Macrophage stimulating protein (MSP) binds to the RON receptor tyrosine kinase.
  • RON activation in macrophages causes shape change and migration.
  • The role of PI-3 kinase in MSP-induced RON signaling in epithelial cells was investigated.

Purpose of the Study:

  • To investigate MSP-induced cell movement in human epithelial cells.
  • To determine the role of phosphatidylinositol-3 (PI-3) kinase in RON-mediated signal transduction.
  • To explore the implications of MSP-stimulated epithelial cell movement.

Main Methods:

  • Studied 125I-MSP binding to RON on epithelial cell lines.
  • Analyzed RON and PI-3 kinase phosphorylation and complex formation.
  • Assessed MSP-induced cell migration and shape change, using wortmannin as an inhibitor.

Main Results:

  • Specific binding of MSP to RON was observed on epithelial cells.
  • MSP induced RON and PI-3 kinase (p85 subunit) tyrosine phosphorylation.
  • MSP stimulated epithelial cell migration, an effect inhibited by wortmannin, indicating PI-3 kinase dependence.

Conclusions:

  • Activation of PI-3 kinase is essential for MSP-induced epithelial cell migration.
  • MSP-stimulated epithelial cell movement has potential implications for wound healing and tumor metastasis.

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