Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes

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

Research output: Contribution to journalArticle

31 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes'. Together they form a unique fingerprint.

  • Cite this

    Awasthi, A., Samarakoon, A., Chu, H., Kamalakannan, R., Quilliam, L. A., Chrzanowska-Wodnicka, M., White, G. C., & 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