title: The mitogen-activated protein kinase scaffold KSR1 is required for recruitment of extracellular signal-regulated kinase to the immunological synapse.
abstract: KSR1 is a mitogen-activated protein (MAP) kinase scaffold that enhances the activation of the MAP kinase extracellular signal-regulated kinase (ERK). The function of KSR1 in NK cell function is not known. Here we show that KSR1 is required for efficient NK-mediated cytolysis and polarization of cytolytic granules. Single-cell analysis showed that ERK is activated in an all-or-none fashion in both wild-type and KSR1-deficient cells. In the absence of KSR1, however, the efficiency of ERK activation is attenuated. Imaging studies showed that KSR1 is recruited to the immunological synapse during T-cell activation and that membrane recruitment of KSR1 is required for recruitment of active ERK to the synapse.
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Giurisato
authors.forename: Joseph
authors.initials: J
authors.lastname: Lin
authors.forename: Angus
authors.initials: A
authors.lastname: Harding
authors.forename: Elisa
authors.initials: E
authors.lastname: Cerutti
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D000818:Animals; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*
chemical_list: D011494:Protein Kinases; C097199:KSR-1 protein kinase; D048049:Extracellular Signal-Regulated MAP Kinases