Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Movement*
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Cell Polarity
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
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Mice
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Mice, Knockout
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Myeloid Cells / enzymology
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Myeloid Cells / physiology*
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Neutrophils / enzymology
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Neutrophils / physiology
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Phagocytes / physiology
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Phosphorylation
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Proto-Oncogene Proteins c-abl / metabolism*
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Proto-Oncogene Proteins c-fyn / genetics
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Proto-Oncogene Proteins c-fyn / metabolism*
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Proto-Oncogene Proteins c-hck / genetics
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Proto-Oncogene Proteins c-hck / metabolism*
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cdc42 GTP-Binding Protein / metabolism
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rac GTP-Binding Proteins / metabolism
Substances
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Hck protein, mouse
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Proto-Oncogene Proteins c-abl
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Proto-Oncogene Proteins c-fyn
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Proto-Oncogene Proteins c-hck
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins