2B4 utilizes ITAM-containing receptor complexes to initiate intracellular signaling and cytolysis

Anya T. Bida, Jadee L. Upshaw Neff, Christopher J. Dick, Renee A. Schoon, Adipong Brickshawana, Claudia C. Chini, Daniel D. Billadeau

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

2B4 is a member of the SLAM receptor family capable of activating NK cell cytotoxicity in the context of EBV infection. SAP (SLAM Associated Protein) deficiency causes defective signaling downstream of SLAM family receptors and high susceptibility to EBV. 2B4 costimulates natural cytotoxicity receptor (NCR) and TCR initiated signals to induce cellular cytotoxicity and cytokine release. The 2B4-SAP signal transduction pathway is not predicted to overlap with the TCR-ITAM pathway, although SAP is required for some TCR-induced signals. We therefore examined the functional relationship between SLAM family receptor 2B4 and ITAM-containing adaptor complexes. Removal of Fce{open}RIγ or CD3ζ-containing complexes, using genetically manipulated cell lines or siRNA specific suppression, significantly reduces 2B4-initiated functions in NK and T cells, respectively. Consistent with this relationship, Syk and ZAP-70 are capable of transducing 2B4 signals for calcium mobilization and cytolysis. Furthermore, ITAM-containing molecules constitutively associate with SAP. These results suggest a potential physical association between 2B4 and the ITAM receptor complexes that is required for 2B4-initiated signaling and cell-mediated killing.

Original languageEnglish (US)
Pages (from-to)1149-1159
Number of pages11
JournalMolecular Immunology
Volume48
Issue number9-10
DOIs
StatePublished - May 2011

Keywords

  • 2B4
  • Cell activation
  • Natural killer cells
  • SAP
  • Signal transduction

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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    Bida, A. T., Upshaw Neff, J. L., Dick, C. J., Schoon, R. A., Brickshawana, A., Chini, C. C., & Billadeau, D. D. (2011). 2B4 utilizes ITAM-containing receptor complexes to initiate intracellular signaling and cytolysis. Molecular Immunology, 48(9-10), 1149-1159. https://doi.org/10.1016/j.molimm.2011.02.008