The mitogen-activated protein kinase scaffold KSR1 is required for recruitment of extracellular signal-regulated kinase to the immunological synapse.
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.
Giurisato
Emanuele
E
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Lin
Joseph
J
Harding
Angus
A
Cerutti
Elisa
E
Cella
Marina
M
Lewis
Robert E
RE
Colonna
Marco
M
Shaw
Andrey S
AS
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*
D011494:Protein Kinases; C097199:KSR-1 protein kinase; D048049:Extracellular Signal-Regulated MAP Kinases