Expression and tyrosine phosphorylation of Cbl regulates macrophage chemokinetic and chemotactic movement

J Cell Physiol. 2003 May;195(2):276-89. doi: 10.1002/jcp.10236.

Abstract

Primary macrophages isolated from hck(-/-)fgr(-/-) mice display altered morphology and F-actin cytoskeletal structures and reduced migration. The ability of phorbol myristyl acetate (PMA), a protein kinase C activator that has been reported to increase macrophage spreading and carcinoma cell motility, to rescue these hck(-/-)fgr(-/-) defects was tested. Although PMA-treated wild-type and hck(-/-)fgr(-/-) macrophages exhibited a similar flattened, spread phenotype, PMA did not rescue the hck(-/-)fgr(-/-) macrophage migration defect. Instead, both PMA-treated wild type and hck(-/-)fgr(-/-) macrophages were defective in spontaneous and chemotactic migration and tyrosine phosphorylation of the Cbl protooncoprotein was decreased in both. Moreover, c-cbl(-/-) macrophages displayed the same impairment of motility as hck(-/-)fgr(-/-) macrophages and a similar morphology with less polarization and more dorsal ruffling than wild-type macrophages. As Hck and Fgr expression and activity were not decreased in c-cbl(-/-) macrophages, these results suggest that Cbl is likely to be an important downstream mediator of the Src family kinase-regulated macrophage motility pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / drug effects
  • Actins / metabolism*
  • Animals
  • Cell Size / drug effects
  • Cell Size / physiology
  • Cells, Cultured
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Mice, Knockout
  • Oncogene Protein v-cbl
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-hck
  • Retroviridae Proteins, Oncogenic / deficiency*
  • Retroviridae Proteins, Oncogenic / drug effects
  • Retroviridae Proteins, Oncogenic / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tyrosine / metabolism
  • src-Family Kinases / drug effects
  • src-Family Kinases / metabolism

Substances

  • Actins
  • Oncogene Protein v-cbl
  • Proto-Oncogene Proteins
  • Retroviridae Proteins, Oncogenic
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Hck protein, mouse
  • Proto-Oncogene Proteins c-hck
  • proto-oncogene proteins c-fgr
  • src-Family Kinases
  • Tetradecanoylphorbol Acetate