Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. J Exp Med 2010 Aug 30;207(9):1923-38
Date
08/25/2010Pubmed ID
20733035Pubmed Central ID
PMC2931159DOI
10.1084/jem.20100040Scopus ID
2-s2.0-77956248916 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
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.
Author List
Awasthi A, Samarakoon A, Chu H, Kamalakannan R, Quilliam LA, Chrzanowska-Wodnicka M, White GC 2nd, Malarkannan SAuthors
Magdalena Chrzanowska PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinSubramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Gilbert C. White MD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCell Movement
Cell Polarity
Cells, Cultured
Cytotoxicity, Immunologic
Killer Cells, Natural
Lymphocyte Function-Associated Antigen-1
Mice
Mice, Knockout
NK Cell Lectin-Like Receptor Subfamily K
Signal Transduction
rap GTP-Binding Proteins
ras GTPase-Activating Proteins
