Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes

Aradhana Awasthi, Asanga Samarakoon, Haiyan Chu, Rajasekaran Kamalakannan, Lawrence Quilliam, Magdalena Chrzanowska-Wodnicka, Gilbert C. White, Subramaniam Malarkannan

Research output: Contribution to journalArticle

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Abstract

Rap1 GTPases control immune synapse formation and signaling in lymphocytes. However, the precise molecular mechanism by which Rap1 regulates natural killer (NK) cell activation is not known. Using Rap1a or Rap1b knockout mice, we identify Rap1b as the major isoform in NK cells. Its absence significantly impaired LFA1 polarization, spreading, and microtubule organizing center (MTOC) formation in NK cells. Neither Rap1 isoform was essential for NK cytotoxicity. However, absence of Rap1b impaired NKG2D, Ly49D, and NCR1-mediated cytokine and chemokine production. Upon activation, Rap1b colocalized with the scaffolding protein IQGAP1. This interaction facilitated sequential phosphorylation of B-Raf, C-Raf, and ERK1/2 and helped IQGAP1 to form a large signalosome in the perinuclear region. These results reveal a previously unrecognized role for Rap1b in NK cell signaling and effector functions.

Original languageEnglish
Pages (from-to)1923-1938
Number of pages16
JournalJournal of Experimental Medicine
Volume207
Issue number9
DOIs
StatePublished - Aug 30 2010

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Natural Killer Cells
Protein Isoforms
Microtubule-Organizing Center
GTP Phosphohydrolases
Chemokines
Knockout Mice
Synapses
Phosphorylation
Lymphocytes
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Awasthi, A., Samarakoon, A., Chu, H., Kamalakannan, R., Quilliam, L., Chrzanowska-Wodnicka, M., ... Malarkannan, S. (2010). Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. Journal of Experimental Medicine, 207(9), 1923-1938. https://doi.org/10.1084/jem.20100040

Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. / Awasthi, Aradhana; Samarakoon, Asanga; Chu, Haiyan; Kamalakannan, Rajasekaran; Quilliam, Lawrence; Chrzanowska-Wodnicka, Magdalena; White, Gilbert C.; Malarkannan, Subramaniam.

In: Journal of Experimental Medicine, Vol. 207, No. 9, 30.08.2010, p. 1923-1938.

Research output: Contribution to journalArticle

Awasthi, A, Samarakoon, A, Chu, H, Kamalakannan, R, Quilliam, L, Chrzanowska-Wodnicka, M, White, GC & Malarkannan, S 2010, 'Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes', Journal of Experimental Medicine, vol. 207, no. 9, pp. 1923-1938. https://doi.org/10.1084/jem.20100040
Awasthi A, Samarakoon A, Chu H, Kamalakannan R, Quilliam L, Chrzanowska-Wodnicka M et al. Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. Journal of Experimental Medicine. 2010 Aug 30;207(9):1923-1938. https://doi.org/10.1084/jem.20100040
Awasthi, Aradhana ; Samarakoon, Asanga ; Chu, Haiyan ; Kamalakannan, Rajasekaran ; Quilliam, Lawrence ; Chrzanowska-Wodnicka, Magdalena ; White, Gilbert C. ; Malarkannan, Subramaniam. / Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. In: Journal of Experimental Medicine. 2010 ; Vol. 207, No. 9. pp. 1923-1938.
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