title: Expression and tyrosine phosphorylation of Cbl regulates macrophage chemokinetic and chemotactic movement.
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.
authors.affiliation: Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Caveggion
authors.forename: Silvia
authors.initials: S
authors.lastname: Continolo
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Pixley
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: David D L
authors.initials: DD
authors.lastname: Bowtell
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Giorgio
authors.initials: G
authors.lastname: Berton
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D050722:Oncogene Protein v-cbl; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D051572:Proto-Oncogene Proteins c-hck; D015682:Retroviridae Proteins, Oncogenic / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D000199:Actins; D050722:Oncogene Protein v-cbl; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C496632:Hck protein, mouse; D051572:Proto-Oncogene Proteins c-hck; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; D013755:Tetradecanoylphorbol Acetate