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

EMBO J. 1999 Jun 1;18(11):3013-23. doi: 10.1093/emboj/18.11.3013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Calcitriol / pharmacology
  • Cell Adhesion / drug effects
  • Cell Differentiation
  • Cell Movement* / drug effects
  • Cytoskeleton / drug effects
  • Enzyme Activation
  • Humans
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Macrophages / metabolism
  • Mice
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / enzymology*
  • Monocytes / metabolism
  • Mutation
  • Phenotype
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-hck
  • Receptors, Cell Surface / metabolism*
  • Receptors, Urokinase Plasminogen Activator
  • Temperature
  • Transfection
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / metabolism
  • Urokinase-Type Plasminogen Activator / pharmacology


  • Actins
  • PLAUR protein, human
  • Plaur protein, mouse
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Transforming Growth Factor beta
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • HCK protein, human
  • Hck protein, mouse
  • Proto-Oncogene Proteins c-hck
  • Urokinase-Type Plasminogen Activator
  • Calcitriol