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Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent

A Danilkovitch1, A Skeel, E J Leonard

  • 1Laboratory of Immunobiology, National Cancer Institute, Frederick, Maryland, 21702, USA. danilkovitch@mail.ncifcrf.gov

Experimental Cell Research
|May 1, 1999
PubMed

Insights

Macrophage stimulating protein (MSP) enhances epithelial cell adhesion by activating phosphatidylinositol 3-kinase (PI3-K), not focal adhesion kinase (FAK). This study reveals PI3-K

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Macrophage stimulating protein (MSP) is a growth and motility factor acting through the RON/STK receptor tyrosine kinase.
  • MSP promotes integrin-dependent epithelial cell migration, suggesting regulation of integrin receptor functions.
  • Integrins are crucial cell surface receptors mediating epithelial cell adhesion and motility via extracellular matrix interactions.

Purpose of the Study:

  • To investigate the enhancement of epithelial cell adhesion by MSP.
  • To elucidate the molecular mechanisms underlying MSP-induced cell adhesion.
  • To determine the roles of phosphatidylinositol 3-kinase (PI3-K) and focal adhesion kinase (FAK) in MSP-mediated adhesion.

Main Methods:

  • Assessed MSP's effect on epithelial cell adhesion to collagen and fibronectin-coated substrates.
  • Utilized RGD-containing peptides to confirm integrin-mediated cell-substrate interactions.
  • Employed wortmannin (PI3-K inhibitor) and dominant-negative FAK constructs to dissect signaling pathways.

Main Results:

  • MSP significantly decreased the time required for 293 and RE7 epithelial cells to adhere to substrates.
  • MSP-induced adhesion was blocked by wortmannin, indicating PI3-K's involvement in the pathway.
  • While MSP induced PI3-K-independent FAK phosphorylation, FAK did not mediate MSP's effects on adhesion or motility.
  • A ligand-independent association between RON and beta1 integrin was observed.

Conclusions:

  • Phosphatidylinositol 3-kinase (PI3-K), but not focal adhesion kinase (FAK), mediates MSP-induced integrin-dependent adhesion in epithelial cells.
  • The findings highlight a critical role for PI3-K in MSP signaling pathways regulating cell adhesion.
  • The observed RON-beta1 integrin association suggests a functional relationship between these receptor systems.

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