| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Release in Human NK Cells Involves Distinct Pathways1
Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107
2B4 (CD244), a member of the CD2 subset of the Ig superfamily
receptors, is expressed on all human NK cells, a subpopulation of T
cells, basophils and monocytes. 2B4 activates NK cell mediated
cytotoxicity, induces secretion of IFN-
and matrix
metalloproteinases, and NK cell invasiveness. Although there has been
several molecules shown to interact with 2B4, the signaling mechanism
of 2B4-mediated activation of NK cells is still unknown. In this study,
we found cross-linking of 2B4 on YT cells, a human NK cell line,
results in the increased DNA binding activity of activator protein-1
(AP-1), an important regulator of nuclear gene expression in
leukocytes. We investigated the possible role of various signaling
molecules that may be involved in the activation of lytic function of
YT cells via 2B4. Treatment of YT cells with various specific
inhibitors indicate that 2B4-stimulation of YT cells in spontaneous and
Ab-dependent cytotoxicity is Ras/Raf dependent and involves multiple
MAPK signaling pathways (ERK1/2 and p38). However, only inhibitors of
transcription and p38 inhibited 2B4-mediated IFN- release indicating
distinct pathways are involved in cytotoxicity and cytokine release. In
this study we also show that 2B4 constitutively associates with the
linker for activation of T cells (LAT) and that 2B4 may mediate NK cell
activation via a LAT-dependent signaling pathway. These results
indicate that 2B4-mediated activation of NK cells involves complex
interactions involving LAT, Ras, Raf, ERK and p38 and that cytolytic
function and cytokine production may be regulated by distinct
pathways.
This article has been cited by other articles:
|
|
 |
|
  N. G. Clarkson and M. H. Brown Inhibition and Activation by CD244 Depends on CD2 and Phospholipase C-{gamma}1 J. Biol. Chem., September 11, 2009; 284(37): 24725 - 24734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Morel and T. Bellon HLA Class I Molecules Regulate IFN-{gamma} Production Induced in NK Cells by Target Cells, Viral Products, or Immature Dendritic Cells through the Inhibitory Receptor ILT2/CD85j J. Immunol., August 15, 2008; 181(4): 2368 - 2381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Malarkannan, J. Regunathan, H. Chu, S. Kutlesa, Y. Chen, H. Zeng, R. Wen, and D. Wang Bcl10 Plays a Divergent Role in NK Cell-Mediated Cytotoxicity and Cytokine Generation J. Immunol., September 15, 2007; 179(6): 3752 - 3762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. D. Wiseman, L. L. Ma, K. J. Marr, G. J. Jones, and C. H. Mody Perforin-Dependent Cryptococcal Microbicidal Activity in NK Cells Requires PI3K-Dependent ERK1/2 Signaling J. Immunol., May 15, 2007; 178(10): 6456 - 6464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Eissmann and C. Watzl Molecular Analysis of NTB-A Signaling: A Role for EAT-2 in NTB-A-Mediated Activation of Human NK Cells. J. Immunol., September 1, 2006; 177(5): 3170 - 3177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sasanuma, A. Tatsuno, S. Hidano, K. Ohshima, Y. Matsuzaki, K. Hayashi, C. A. Lowell, D. Kitamura, and R. Goitsuka Dual function for the adaptor MIST in IFN-{gamma} production by NK and CD4+NKT cells regulated by the Src kinase Fgr Blood, May 1, 2006; 107(9): 3647 - 3655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Jiang, B. A. Orr, D. M. Kranz, and D. J. Shapiro Estrogen Induction of the Granzyme B Inhibitor, Proteinase Inhibitor 9, Protects Cells against Apoptosis Mediated by Cytotoxic T Lymphocytes and Natural Killer Cells Endocrinology, March 1, 2006; 147(3): 1419 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Saborit-Villarroya, J. M. Del Valle, X. Romero, E. Esplugues, P. Lauzurica, P. Engel, and M. Martin The Adaptor Protein 3BP2 Binds Human CD244 and Links this Receptor to Vav Signaling, ERK Activation, and NK Cell Killing J. Immunol., October 1, 2005; 175(7): 4226 - 4235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Morandi, R. Costa, M. Falco, S. Parolini, A. De Maria, G. Ratto, M. C. Mingari, G. Melioli, A. Moretta, and G. Ferlazzo Distinctive Lack of CD48 Expression in Subsets of Human Dendritic Cells Tunes NK Cell Activation J. Immunol., September 15, 2005; 175(6): 3690 - 3697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Maghazachi Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells Pharmacol. Rev., September 1, 2005; 57(3): 339 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Martin, J. M. Del Valle, I. Saborit, and P. Engel Identification of Grb2 As a Novel Binding Partner of the Signaling Lymphocytic Activation Molecule-Associated Protein Binding Receptor CD229 J. Immunol., May 15, 2005; 174(10): 5977 - 5986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aoukaty and R. Tan Role for Glycogen Synthase Kinase-3 in NK Cell Cytotoxicity and X-Linked Lymphoproliferative Disease J. Immunol., April 15, 2005; 174(8): 4551 - 4558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Vaidya, S. E. Stepp, M. E. McNerney, J.-K. Lee, M. Bennett, K.-M. Lee, C. L. Stewart, V. Kumar, and P. A. Mathew Targeted Disruption of the 2B4 Gene in Mice Reveals an In Vivo Role of 2B4 (CD244) in the Rejection of B16 Melanoma Cells J. Immunol., January 15, 2005; 174(2): 800 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Munitz, I. Bachelet, S. Fraenkel, G. Katz, O. Mandelboim, H.-U. Simon, L. Moretta, M. Colonna, and F. Levi-Schaffer 2B4 (CD244) Is Expressed and Functional on Human Eosinophils J. Immunol., January 1, 2005; 174(1): 110 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mavropoulos, G. Sully, A. P. Cope, and A. R. Clark Stabilization of IFN-{gamma} mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells Blood, January 1, 2005; 105(1): 282 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Roda-Navarro, M. Mittelbrunn, M. Ortega, D. Howie, C. Terhorst, F. Sanchez-Madrid, and E. Fernandez-Ruiz Dynamic Redistribution of the Activating 2B4/SAP Complex at the Cytotoxic NK Cell Immune Synapse J. Immunol., September 15, 2004; 173(6): 3640 - 3646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-M. Lee, M. E. McNerney, S. E. Stepp, P. A. Mathew, J. D. Schatzle, M. Bennett, and V. Kumar 2B4 Acts As a Non-Major Histocompatibility Complex Binding Inhibitory Receptor on Mouse Natural Killer Cells J. Exp. Med., May 3, 2004; 199(9): 1245 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vankayalapati, P. Klucar, B. Wizel, S. E. Weis, B. Samten, H. Safi, H. Shams, and P. F. Barnes NK Cells Regulate CD8+ T Cell Effector Function in Response to an Intracellular Pathogen J. Immunol., January 1, 2004; 172(1): 130 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N. Baxevanis, A. D. Gritzapis, and M. Papamichail In Vivo Antitumor Activity of NKT Cells Activated by the Combination of IL-12 and IL-18 J. Immunol., September 15, 2003; 171(6): 2953 - 2959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Tangye, K. E. Nichols, N. J. Hare, and B. C. M. van de Weerdt Functional Requirements for Interactions Between CD84 and Src Homology 2 Domain-Containing Proteins and Their Contribution to Human T Cell Activation J. Immunol., September 1, 2003; 171(5): 2485 - 2495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Gu, A. Laouar, J. Wan, M. Daheshia, J. Lieberman, W. M. Yokoyama, H. R. Katz, and N. Manjunath The gp49B1 Inhibitory Receptor Regulates the IFN-{gamma} Responses of T Cells and NK Cells J. Immunol., April 15, 2003; 170(8): 4095 - 4101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Watzl and E. O. Long Natural Killer Cell Inhibitory Receptors Block Actin Cytoskeleton-dependent Recruitment of 2B4 (CD244) to Lipid Rafts J. Exp. Med., January 6, 2003; 197(1): 77 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Klem, P. C. Verrett, V. Kumar, and J. D. Schatzle 2B4 Is Constitutively Associated with Linker for the Activation of T Cells in Glycolipid-Enriched Microdomains: Properties Required for 2B4 Lytic Function J. Immunol., July 1, 2002; 169(1): 55 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Yusa, T. L. Catina, and K. S. Campbell SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells J. Immunol., May 15, 2002; 168(10): 5047 - 5057. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
