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

Journal of Leukocyte Biology

James H. Steer¹  Eloise L. Greenland¹  David A. Joyce¹  Fiona J. Pixley¹  Andrew J. Sunderland¹  Kellie A. Mouchemore¹  Natalia G. Sampaio¹  Amy R. Dwyer¹ 

[1] School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, AustraliaSchool of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, AustraliaSchool of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia

关键词: protein kinases/phosphatases;    chemotaxis;    invasion;    signal transduction;   

DOI  :  10.1189/jlb.2A0815-344RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown