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The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration

Massimo M Santoro1, Giovanni Gaudino, Pier Carlo Marchisio

  • 1Department of Medical Sciences, University of Piemonte Orientale "A. Avogadro", 28100, Novara, Italy. msantoro@med.unipmn.it

Developmental Cell
|August 16, 2003
PubMed

Insights

Macrophage stimulating protein (MSP) signaling transforms alpha6beta4 integrin from an adhesion molecule into a signaling component, crucial for keratinocyte migration and epidermal wound healing.

Area of Science:

  • Cell Biology
  • Dermatology
  • Molecular Biology

Background:

  • Growth factors, integrins, and the extracellular matrix (ECM) are vital for skin repair.
  • The precise interactions governing these components during epidermal wound healing remain unclear.

Purpose of the Study:

  • To elucidate the role of macrophage stimulating protein (MSP) and its receptor Ron in keratinocyte behavior during wound healing.
  • To investigate the functional switch of alpha6beta4 integrin mediated by MSP-Ron signaling.

Main Methods:

  • Investigated growth factor-receptor signaling pathways in keratinocytes.
  • Utilized phosphorylation site analysis and protein complex formation studies.
  • Examined integrin localization and cell migration assays on laminin-5.

Main Results:

  • MSP-Ron signaling induces phosphorylation of Ron and alpha6beta4 integrin at 14-3-3 binding sites.
  • This leads to the formation of a Ron/alpha6beta4 complex, displacing alpha6beta4 from hemidesmosomes to lamellipodia.
  • Activation of alpha3beta1 integrin, keratinocyte spreading, migration, and downstream signaling pathways (p38, NF-kappaB) were observed.

Conclusions:

  • MSP-Ron signaling triggers a functional transformation of alpha6beta4 integrin from a structural adhesive protein to a signaling molecule.
  • This mechanism is critical for keratinocyte migration and plays a significant role in human epidermal wound healing.

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