title: Cytokine-induced macropinocytosis in macrophages is regulated by 14-3-3ζ through its interaction with serine-phosphorylated coronin 1.
abstract: 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.
authors: Biozentrum, University of Basel, Switzerland.
authors: Somdeb
authors: S
authors: BoseDasgupta
authors: Suzette
authors: S
authors: Moes
authors: Paul
authors: P
authors: Jenoe
authors: Jean
authors: J
authors: Pieters
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000502:physiology*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism*; D009163:Mycobacterium bovis / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010873:Pinocytosis; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D000075370:Receptors for Activated C Kinase
chemical_list: D048948:14-3-3 Proteins; D016207:Cytokines; D008840:Microfilament Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; C090294:RACK1 protein, mouse; D000075370:Receptors for Activated C Kinase; C072061:coronin proteins
keywords: 14-3-3ζ; coronin 1; macrophage; macropinocytosis; receptor of activated C kinase 1