Protein kinase c-θ clustering at immunological synapses amplifies effector responses in NK cells Journal Article
| Authors: | Merino, E. ; Abeyweera, T. P.; Firth, M. A.; Zawislak, C. L.; Basu, R.; Liu, X.; Sun, J. C.; Huse, M. |
| Article Title: | Protein kinase c-θ clustering at immunological synapses amplifies effector responses in NK cells |
| Abstract: | In lymphocytes, stimulation of cell surface activating receptors induces the formation of protein microclusters at the plasma membrane that contain the receptor itself, along with other signaling molecules. Although these microclusters are generally thought to be crucial for promoting downstream cellular responses, evidence that specifically links clustering potential to signaling output is lacking.We found that protein kinase C-θ (PKCθ), a key signaling molecule in multiple lymphocyte subsets, formed microclusters in activated NK cells. These microclusters coalesced within the immunological synapse between the NK cell and its target cell. Clustering was mediated by the regulatory region of PKCθ and specifically required a putative phosphotyrosine-binding site within its N-terminal C2 domain. Whereas expression of wild-type PKCθ rescued the cytokine production defect displayed by PKCu-deficient NK cells, expression of a PKCθ point-mutant incapable of forming microclusters had little to no effect. Hence, PKCθ clustering was necessary for optimal effector function. Notably, only receptors containing ITAMs induced PKCθ microclusters on their own, explaining previous observations that ITAM-coupled receptors promote stronger activating signals and effector responses than do receptors lacking these motifs. Taken together, our results provide a cell biological basis for the role of PKCθ clustering during NK cell activation, and highlight the importance of subcellular compartmentalization for lymphocyte signal transduction. Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein expression; protein phosphorylation; nonhuman; protein domain; animal cell; mouse; animals; mice; cell compartmentalization; mutational analysis; lymphocyte activation; amino terminal sequence; cellular distribution; natural killer cell; killer cells, natural; binding site; cytokine production; effector cell; protein structure, tertiary; protein kinase c; point mutation; protein cross linking; t lymphocyte activation; immunological synapses; isoenzymes; amino acid motifs; phosphotyrosine; immunological synapse; protein kinase c theta; nucleotide binding site |
| Journal Title: | Journal of Immunology |
| Volume: | 189 |
| Issue: | 10 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2012-11-15 |
| Start Page: | 4859 |
| End Page: | 4869 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1200825 |
| PROVIDER: | scopus |
| PUBMED: | 23077238 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 December 2012" - "CODEN: JOIMA" - "Source: Scopus" |
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