c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration.
Cytoskeleton dynamics are regulated by Src-family tyrosine kinases (SFKs) and c-Abl. We found that the SFK members Hck and c-Fgr regulate tyrosine phosphorylation of c-Abl and c-Abl associates with beta1 integrin-bound Hck or c-Fgr in murine macrophages. Studies with selective inhibitors and cells from SFK-deficient mice showed that c-Abl and SFK regulate migration and activation of the small GTPases Cdc42 and Rac in macrophages. Additionally, human neutrophil chemotactic activity was reduced by c-Abl inhibitors, and neutrophils from chronic myeloid leukaemia patients displayed an increased chemotactic ability. Hence, Src-family kinase and c-Abl cross-talk in the regulation of myeloid cell migration.
Baruzzi
Anna
A
Department of Pathology, University of Verona, Verona, Italy.
Iacobucci
Ilaria
I
Soverini
Simona
S
Lowell
Clifford A
CA
Martinelli
Giovanni
G
Berton
Giorgio
G
D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000201:enzymology / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D010586:Phagocytes / Q000502:physiology; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
C496632:Hck protein, mouse; D016315:Proto-Oncogene Proteins c-abl; D051076:Proto-Oncogene Proteins c-fyn; D051572:Proto-Oncogene Proteins c-hck; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins