Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence

Ferdinando Chiaradonna, Laura Fontana, Carlo Iavarone, M. Vincenza Carriero, Glen Scholz, M. Vittoria Barone, M. Patrizia Stoppelli

Research output: Contribution to journalArticle

Abstract

Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed, U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.

Original languageEnglish
Pages (from-to)3013-3023
Number of pages11
JournalEMBO Journal
Volume18
Issue number11
DOIs
Publication statusPublished - Jun 1 1999

Keywords

  • Cell motility and adhesion
  • Cytoskeleton
  • Myelomonocytic differentiation
  • Src kinases
  • Urokinase receptor signalling

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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