Src family kinase expression and subcellular localization in macrophages: Implications for their role in CSF-1-induced macrophage migration

Amy R. Dwyer, Kellie A. Mouchemore, James H. Steer, Andrew J. Sunderland, Natalia G. Sampaio, Eloise L. Greenland, David A. Joyce, Fiona J. Pixley

Research output: Contribution to journalArticlepeer-review

16 Citations (Web of Science)

Abstract

© Society for Leukocyte Biology.
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 colonystimulating factor-1 signaling, and we have shown previously that phosphatidylinositol 3-kinase p110d 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 colonystimulating 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 colonystimulating 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 colonystimulating 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.
Original languageEnglish
Pages (from-to)163-175
Number of pages13
JournalJournal of Leukocyte Biology
Volume100
Issue number1
Early online date8 Jan 2016
DOIs
Publication statusPublished - Jul 2016

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