First Author | Caveggion E | Year | 2003 |
Journal | J Cell Physiol | Volume | 195 |
Issue | 2 | Pages | 276-89 |
PubMed ID | 12652654 | Mgi Jnum | J:82782 |
Mgi Id | MGI:2655028 | Doi | 10.1002/jcp.10236 |
Citation | Caveggion E, et al. (2003) Expression and tyrosine phosphorylation of Cbl regulates macrophage chemokinetic and chemotactic movement. J Cell Physiol 195(2):276-89 |
abstractText | 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. |