title: Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF-1-induced macrophage migration.
abstract: A major role of colony-stimulating factor-1 is to stimulate the differentiation of mononuclear phagocytic lineage cells into adherent, motile, mature macrophages. The colony-stimulating factor-1 receptor transduces colony-stimulating factor-1 signaling, and we have shown previously that phosphatidylinositol 3-kinase p110δ is a critical mediator of colony-stimulating factor-1-stimulated motility through the colony-stimulating factor-1 receptor pY721 motif. Src family kinases are also implicated in the regulation of macrophage motility and in colony-stimulating factor-1 receptor signaling, although functional redundancy of the multiple SFKs expressed in macrophages makes it challenging to delineate their specific functions. We report a comprehensive analysis of individual Src family kinase expression in macrophage cell lines and primary macrophages and demonstrate colony-stimulating factor-1-induced changes in Src family kinase subcellular localization, which provides clues to their distinct and redundant functions in macrophages. Moreover, expression of individual Src family kinases is both species specific and dependent on colony-stimulating factor-1-induced macrophage differentiation. Hck associated with the activated colony-stimulating factor-1 receptor, whereas Lyn associated with the receptor in a constitutive manner. Consistent with this, inhibitor studies revealed that Src family kinases were important for both colony-stimulating factor-1 receptor activation and colony-stimulating factor-1-induced macrophage spreading, motility, and invasion. Distinct colony-stimulating factor-1-induced changes in the subcellular localization of individual SFKs suggest specific roles for these Src family kinases in the macrophage response to colony-stimulating factor-1.
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Dwyer
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Mouchemore
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: James H
authors.initials: JH
authors.lastname: Steer
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sunderland
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Natalia G
authors.initials: NG
authors.lastname: Sampaio
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Eloise L
authors.initials: EL
authors.lastname: Greenland
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Joyce
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia fiona.pixley@uwa.edu.au.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Pixley
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D019061:src-Family Kinases
keywords: chemotaxis; invasion; protein kinases/phosphatases; signal transduction