Premium
Expression and tyrosine phosphorylation of Cbl regulates macrophage chemokinetic and chemotactic movement
Author(s) -
Caveggion Elena,
Continolo Silvia,
Pixley Fiona J.,
Stanley E. Richard,
Bowtell David D.L.,
Lowell Clifford A.,
Berton Giorgio
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10236
Subject(s) - phosphorylation , chemotaxis , tyrosine phosphorylation , microbiology and biotechnology , macrophage , tyrosine , movement (music) , chemistry , biology , biochemistry , in vitro , receptor , art , aesthetics
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. © 2003 Wiley‐Liss, Inc.