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

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 phosphatidyl...

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Main Authors: Dwyer, AR, Mouchemore, KA, Steer, JH, Sunderland, AJ, Sampaio, N, Greenland, EL, Joyce, DA, Pixley, FJ
Format: Journal article
Language:English
Published: Wiley 2016
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author Dwyer, AR
Mouchemore, KA
Steer, JH
Sunderland, AJ
Sampaio, N
Greenland, EL
Joyce, DA
Pixley, FJ
author_facet Dwyer, AR
Mouchemore, KA
Steer, JH
Sunderland, AJ
Sampaio, N
Greenland, EL
Joyce, DA
Pixley, FJ
author_sort Dwyer, AR
collection OXFORD
description 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.
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spelling oxford-uuid:a52314c6-b897-4032-9d2b-ed4ddb271fc42025-01-03T07:42:35ZSrc family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migrationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a52314c6-b897-4032-9d2b-ed4ddb271fc4EnglishSymplectic Elements at OxfordWiley2016Dwyer, ARMouchemore, KASteer, JHSunderland, AJSampaio, NGreenland, ELJoyce, DAPixley, FJA 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.
spellingShingle Dwyer, AR
Mouchemore, KA
Steer, JH
Sunderland, AJ
Sampaio, N
Greenland, EL
Joyce, DA
Pixley, FJ
Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migration
title Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migration
title_full Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migration
title_fullStr Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migration
title_full_unstemmed Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migration
title_short Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF‐1‐induced macrophage migration
title_sort src family kinase expression and subcellular localization in macrophages implications for their role in csf 1 induced macrophage migration
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