HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ljutic, B. Articles by Zúñiga-Pflücker, J. C. Search for Related Content PubMed PubMed Citation Articles by Ljutic, B. Articles by Zúñiga-Pflücker, J. C.

Functional Requirements for Signaling through the Stimulatory and Inhibitory Mouse NKR-P1 (CD161) NK Cell Receptors¹

Department of Immunology, University of Toronto, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada

The NK cell receptor protein 1 (NKR-P1) (CD161) molecules represent a family of type II transmembrane C-type lectin-like receptors expressed predominantly by NK cells. Despite sharing a common NK1.1 epitope, the mouse NKR-P1B and NKR-P1C receptors possess opposing functions in NK cell signaling. Engagement of NKR-P1C stimulates cytotoxicity of target cells, Ca²⁺ flux, phosphatidylinositol turnover, kinase activity, and cytokine production. In contrast, NKR-P1B engagement inhibits NK cell cytotoxicity. Nonetheless, it remains unclear how different signaling outcomes are mediated at the molecular level. Here, we demonstrate that both NKR-P1B and NKR-P1C associate with the tyrosine kinase, p56^lck. The interaction is mediated through the di-cysteine CxCP motif in the cytoplasmic domains of NKR-P1B/C. Disrupting this motif leads to abrogation of both stimulatory and inhibitory NKR-P1 signals. In addition, mutation of the consensus ITIM (LxYxxL) in NKR-P1B abolishes both its Src homology 2-containing protein tyrosine phosphatase-1 recruitment and inhibitory function. Strikingly, engagement of NKR-P1C on NK cells obtained from Lck-deficient mice failed to induce NK cytotoxicity. These results reveal a role for Lck in the initiation of NKR-P1 signals, and demonstrate a requirement for the ITIM in NKR-P1-mediated inhibition.

This article has been cited by other articles:

				M. M. Amaral, C. Davio, A. Ceballos, G. Salamone, C. Canones, J. Geffner, and M. Vermeulen Histamine Improves Antigen Uptake and Cross-Presentation by Dendritic Cells J. Immunol., September 15, 2007; 179(6): 3425 - 3433. [Abstract] [Full Text] [PDF]

				S. Ravet, D. Scott-Algara, E. Bonnet, H. K. Tran, T. Tran, N. Nguyen, L. X. Truong, I. Theodorou, F. Barre-Sinoussi, G. Pancino, et al. Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals Blood, May 15, 2007; 109(10): 4296 - 4305. [Abstract] [Full Text] [PDF]

				J. R. Carlyle, A. Mesci, B. Ljutic, S. Belanger, L.-H. Tai, E. Rousselle, A. D. Troke, M.-F. Proteau, and A. P. Makrigiannis Molecular and Genetic Basis for Strain-Dependent NK1.1 Alloreactivity of Mouse NK Cells. J. Immunol., June 15, 2006; 176(12): 7511 - 7524. [Abstract] [Full Text] [PDF]

				D. Pozo, M. Vales-Gomez, N. Mavaddat, S. C. Williamson, S. E. Chisholm, and H. Reyburn CD161 (Human NKR-P1A) Signaling in NK Cells Involves the Activation of Acid Sphingomyelinase J. Immunol., February 15, 2006; 176(4): 2397 - 2406. [Abstract] [Full Text] [PDF]