Abstract
Primary macrophages isolated from hck^β/β^fgr^β/β^ mice display altered morphology and Fβactin 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^β/β^fgr^β/β^ defects was tested. Although PMAβtreated wildβtype and hck^β/β^fgr^β/β^ macrophages exhibited a similar flattened, spread phenotype, PMA did not rescue the hck^β/β^fgr^β/β^ macrophage migration defect. Instead, both PMAβtreated wild type and hck^β/β^fgr^β/β^ macrophages were defective in spontaneous and chemotactic migration and tyrosine phosphorylation of the Cbl protooncoprotein was decreased in both. Moreover, cβcbl^β/β^ macrophages displayed the same impairment of motility as hck^β/β^fgr^β/β^ macrophages and a similar morphology with less polarization and more dorsal ruffling than wildβtype macrophages. As Hck and Fgr expression and activity were not decreased in cβcbl^β/β^ macrophages, these results suggest that Cbl is likely to be an important downstream mediator of the Src family kinaseβregulated macrophage motility pathway. Β© 2003 WileyβLiss, Inc.