Cytokine-induced macropinocytosis in macrophages is regulated by 14-3-3ζ through its interaction with serine-phosphorylated coronin 1.
The induction of macropinocytosis in macrophages during an inflammatory response is important for clearance of pathogenic microbes as well as the generation of appropriate immune responses. Recent data suggest that cytokine stimulation of macrophages induces macropinocytosis through phosphorylation of the protein coronin 1, thereby redistributing coronin 1 from the cell cortex to the cytoplasm followed by the activation of phosphoinositol-3 (PI-3) kinase. However, how coronin 1 phosphorylation regulates these processes remains unclear. We here define an essential role for 14-3-3ζ in cytokine-induced and coronin-1-dependent macropinocytosis in macrophages. We found that, upon stimulation, phosphorylated coronin 1 transiently associated with 14-3-3ζ and receptor of activated C kinase 1 (RACK1). Importantly, downregulation of 14-3-3ζ, but not RACK1, prevented relocation of coronin 1, as well as the induction of PI-3 kinase activity and thereby macropinocytosis upon cytokine stimulation. Together these data define an essential role for 14-3-3ζ in the regulation of macropinocytosis in macrophages upon cytokine stimulation through modulation of the localization of coronin 1.
['BoseDasgupta|Somdeb|S|', 'Moes|Suzette|S|', 'Jenoe|Paul|P|', 'Pieters|Jean|J|']
D048948:14-3-3 Proteins D000818:Animals D002460:Cell Line D016207:Cytokines D008262:Macrophage Activation D008264:Macrophages D008822:Mice, Transgenic D008840:Microfilament Proteins D009163:Mycobacterium bovis D009479:Neuropeptides D010750:Phosphoproteins D010766:Phosphorylation D010873:Pinocytosis D011499:Protein Processing, Post-Translational D021381:Protein Transport D000075370:Receptors for Activated C Kinase
macropinocytosis macrophage 14-3-3ζ coronin 1 receptor of activated C kinase 1