| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Fox Chase Cancer Center, Division of Basic Science, Institute for Cancer Research, Philadelphia, PA 19111
Killer cell Ig-like receptors (KIR) are MHC class I-binding
immunoreceptors that can suppress activation of human NK cells through
recruitment of the Src homology 2-containing protein tyrosine
phosphatase-1 (SHP-1) to two immunoreceptor tyrosine-based inhibitory
motifs (ITIMs) in their cytoplasmic domains. KIR2DL4 (2DL4; CD158d) is
a structurally distinct member of the KIR family, which is expressed on
most, if not all, human NK cells. 2DL4 contains only one ITIM in its
cytoplasmic domain and an arginine in its transmembrane region,
suggesting both inhibitory and activating functions. While 2DL4 can
activate IFN-
production, dependent upon the transmembrane arginine,
the function of the single ITIM of 2DL4 remains unknown. In this study,
tandem ITIMs of KIR3DL1 (3DL1) and the single ITIM of 2DL4 were
directly compared in functional and biochemical assays. Using a
retroviral transduction method, we show in human NK cell lines that 1)
the single ITIM of 2DL4 efficiently inhibits natural cytotoxicity
responses; 2) the phosphorylated single ITIM recruits SHP-2 protein
tyrosine phosphatase, but not SHP-1 in NK cells; 3) expression of
dominant-negative SHP-1 does not block the ability of 2DL4 to inhibit
natural cytotoxicity; 4) surprisingly, mutation of the tyrosine within
the single ITIM does not completely abolish inhibitory function; and 5)
this correlates with weak SHP-2 binding to the mutant ITIM of 2DL4 in
NK cells and a corresponding nonphosphorylated ITIM peptide in vitro.
These results reveal new aspects of the KIR-inhibitory pathway in human
NK cells, which are SHP-1 and phosphotyrosine
independent.
This article has been cited by other articles:
|
|
 |
|
  J. Giustiniani, A. Bensussan, and A. Marie-Cardine Identification and Characterization of a Transmembrane Isoform of CD160 (CD160-TM), a Unique Activating Receptor Selectively Expressed upon Human NK Cell Activation J. Immunol., January 1, 2009; 182(1): 63 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fourmentraux-Neves, A. Jalil, S. Da Rocha, C. Pichon, S. Chouaib, G. Bismuth, and A. Caignard Two opposite signaling outputs are driven by the KIR2DL1 receptor in human CD4+ T cells Blood, September 15, 2008; 112(6): 2381 - 2389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. MacFarlane IV, T. Yamazaki, M. Fang, L. J. Sigal, T. Kurosaki, and K. S. Campbell Enhanced NK-cell development and function in BCAP-deficient mice Blood, July 1, 2008; 112(1): 131 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Carosella, B. Favier, N. Rouas-Freiss, P. Moreau, and J. LeMaoult Beyond the increasing complexity of the immunomodulatory HLA-G molecule Blood, May 15, 2008; 111(10): 4862 - 4870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Binyamin, R. K. Alpaugh, T. L. Hughes, C. T. Lutz, K. S. Campbell, and L. M. Weiner Blocking NK Cell Inhibitory Self-Recognition Promotes Antibody-Dependent Cellular Cytotoxicity in a Model of Anti-Lymphoma Therapy J. Immunol., May 1, 2008; 180(9): 6392 - 6401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Meyaard The inhibitory collagen receptor LAIR-1 (CD305) J. Leukoc. Biol., April 1, 2008; 83(4): 799 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Shahjahan Miah, T. L. Hughes, and K. S. Campbell KIR2DL4 Differentially Signals Downstream Functions in Human NK Cells through Distinct Structural Modules J. Immunol., March 1, 2008; 180(5): 2922 - 2932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Alvarez-Arias and K. S. Campbell Protein Kinase C Regulates Expression and Function of Inhibitory Killer Cell Ig-Like Receptors in NK Cells J. Immunol., October 15, 2007; 179(8): 5281 - 5290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Estefania, R. Flores, N. Gomez-Lozano, H. Aguilar, M. Lopez-Botet, and C. Vilches Human KIR2DL5 Is an Inhibitory Receptor Expressed on the Surface of NK and T Lymphocyte Subsets J. Immunol., April 1, 2007; 178(7): 4402 - 4410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Alvarez-Errico, J. Sayos, and M. Lopez-Botet The IREM-1 (CD300f) Inhibitory Receptor Associates with the p85{alpha} Subunit of Phosphoinositide 3-Kinase J. Immunol., January 15, 2007; 178(2): 808 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Kirwan and D. N. Burshtyn Killer Cell Ig-Like Receptor-Dependent Signaling by Ig-Like Transcript 2 (ILT2/CD85j/LILRB1/LIR-1) J. Immunol., October 15, 2005; 175(8): 5006 - 5015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Avril, S. D. Freeman, H. Attrill, R. G. Clarke, and P. R. Crocker Siglec-5 (CD170) Can Mediate Inhibitory Signaling in the Absence of Immunoreceptor Tyrosine-based Inhibitory Motif Phosphorylation J. Biol. Chem., May 20, 2005; 280(20): 19843 - 19851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kikuchi-Maki, T. L. Catina, and K. S. Campbell Cutting Edge: KIR2DL4 Transduces Signals into Human NK Cells through Association with the Fc Receptor {gamma} Protein J. Immunol., April 1, 2005; 174(7): 3859 - 3863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Draghi, N. Yawata, M. Gleimer, M. Yawata, N. M. Valiante, and P. Parham Single-cell analysis of the human NK cell response to missing self and its inhibition by HLA class I Blood, March 1, 2005; 105(5): 2028 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Shahied, Y. Tang, R. K. Alpaugh, R. Somer, D. Greenspon, and L. M. Weiner Bispecific Minibodies Targeting HER2/neu and CD16 Exhibit Improved Tumor Lysis When Placed in a Divalent Tumor Antigen Binding Format J. Biol. Chem., December 24, 2004; 279(52): 53907 - 53914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Avril, H. Floyd, F. Lopez, E. Vivier, and P. R. Crocker The Membrane-Proximal Immunoreceptor Tyrosine-Based Inhibitory Motif Is Critical for the Inhibitory Signaling Mediated by Siglecs-7 and -9, CD33-Related Siglecs Expressed on Human Monocytes and NK Cells J. Immunol., December 1, 2004; 173(11): 6841 - 6849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Yusa, T. L. Catina, and K. S. Campbell KIR2DL5 Can Inhibit Human NK Cell Activation Via Recruitment of Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP-2) J. Immunol., June 15, 2004; 172(12): 7385 - 7392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Lebbink, T. de Ruiter, A. Verbrugge, W. S. Bril, and L. Meyaard The Mouse Homologue of the Leukocyte-Associated Ig-Like Receptor-1 Is an Inhibitory Receptor That Recruits Src Homology Region 2-Containing Protein Tyrosine Phosphatase (SHP)-2, but Not SHP-1 J. Immunol., May 1, 2004; 172(9): 5535 - 5543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Campbell, S.-i. Yusa, A. Kikuchi-Maki, and T. L. Catina NKp44 Triggers NK Cell Activation through DAP12 Association That Is Not Influenced by a Putative Cytoplasmic Inhibitory Sequence J. Immunol., January 15, 2004; 172(2): 899 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Verbrugge, T. d. Ruiter, H. Clevers, and L. Meyaard Differential contribution of the immunoreceptor tyrosine-based inhibitory motifs of human leukocyte-associated Ig-like receptor-1 to inhibitory function and phosphatase recruitment Int. Immunol., November 1, 2003; 15(11): 1349 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kikuchi-Maki, S.-i. Yusa, T. L. Catina, and K. S. Campbell KIR2DL4 Is an IL-2-Regulated NK Cell Receptor That Exhibits Limited Expression in Humans but Triggers Strong IFN-{gamma} Production J. Immunol., October 1, 2003; 171(7): 3415 - 3425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Goodridge, C. S. Witt, F. T. Christiansen, and H. S. Warren KIR2DL4 (CD158d) Genotype Influences Expression and Function in NK Cells J. Immunol., August 15, 2003; 171(4): 1768 - 1774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Yusa and K. S. Campbell Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP-2) Can Play a Direct Role in the Inhibitory Function of Killer Cell Ig-Like Receptors in Human NK Cells J. Immunol., May 1, 2003; 170(9): 4539 - 4547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, B. A. Rabinovich, R. Hurren, J. Shannon, and R. G. Miller Expression cloning and function of the rat NK activating and inhibitory receptors NKR-P1A and -P1B Int. Immunol., March 1, 2003; 15(3): 411 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Faure and E. O. Long KIR2DL4 (CD158d), an NK Cell-Activating Receptor with Inhibitory Potential J. Immunol., June 15, 2002; 168(12): 6208 - 6214. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
