| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
DNAX Research Institute, Palo Alto, CA 94304
CD200 and its receptor CD200R are both type I membrane glycoproteins that contain two Ig-like domains. Engagement of CD200R by CD200 inhibits activation of myeloid cells. Unlike the majority of immune inhibitory receptors, CD200R lacks an ITIM in the cytoplasmic domain. The molecular mechanism of CD200R inhibition of myeloid cell activation is unknown. In this study, we examined the CD200R signaling pathways that control degranulation of mouse bone marrow-derived mast cells. We found that upon ligand binding, CD200R is phosphorylated on tyrosine and subsequently binds to adapter proteins Dok1 and Dok2. Upon phosphorylation, Dok1 binds to SHIP and both Dok1 and Dok2 recruit RasGAP, which mediates the inhibition of the Ras/MAPK pathways. Activation of ERK, JNK, and p38 MAPK are all inhibited by CD200R engagement. The reduced activation of these MAPKs is responsible for the observed inhibition of mast cell degranulation and cytokine production. Similar signaling events were also observed upon CD200R engagement in mouse peritoneal cells. These data define a novel inhibitory pathway used by CD200R in modulating mast cell function and help to explain how engagement of this receptor in vivo regulates myeloid cell function.
This article has been cited by other articles:
|
|
 |
|
  R. Mihrshahi, A. N. Barclay, and M. H. Brown Essential Roles for Dok2 and RasGAP in CD200 Receptor-Mediated Regulation of Human Myeloid Cells J. Immunol., October 15, 2009; 183(8): 4879 - 4886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhang, M. Stanford, J. Liu, C. Barrett, L. Jiang, A. N. Barclay, and G. McFadden Inhibition of Macrophage Activation by the Myxoma Virus M141 Protein (vCD200) J. Virol., September 15, 2009; 83(18): 9602 - 9607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Gorczynski, Z. Chen, W. He, I. Khatri, Y. Sun, K. Yu, and I. Boudakov Expression of a CD200 Transgene Is Necessary for Induction but Not Maintenance of Tolerance to Cardiac and Skin Allografts J. Immunol., August 1, 2009; 183(3): 1560 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gorczynski, I. Khatri, L. Lee, and I. Boudakov An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells J. Immunol., May 1, 2008; 180(9): 5946 - 5955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kojima, K. Obata, K. Mukai, S. Sato, T. Takai, Y. Minegishi, and H. Karasuyama Mast Cells and Basophils Are Selectively Activated In Vitro and In Vivo through CD200R3 in an IgE-Independent Manner J. Immunol., November 15, 2007; 179(10): 7093 - 7100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Copland, C. J. Calder, B. J.E. Raveney, L. B. Nicholson, J. Phillips, H. Cherwinski, M. Jenmalm, J. D. Sedgwick, and A. D. Dick Monoclonal Antibody-Mediated CD200 Receptor Signaling Suppresses Macrophage Activation and Tissue Damage in Experimental Autoimmune Uveoretinitis Am. J. Pathol., August 1, 2007; 171(2): 580 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Chitnis, J. Imitola, Y. Wang, W. Elyaman, P. Chawla, M. Sharuk, K. Raddassi, R. T. Bronson, and S. J. Khoury Elevated Neuronal Expression of CD200 Protects Wlds Mice from Inflammation-Mediated Neurodegeneration Am. J. Pathol., May 1, 2007; 170(5): 1695 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. R. Rezaee, C. Cunningham, A. J. Davison, and D. J. Blackbourn Kaposi's sarcoma-associated herpesvirus immune modulation: an overview J. Gen. Virol., July 1, 2006; 87(7): 1781 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhang and J. H. Phillips Identification of tyrosine residues crucial for CD200R-mediated inhibition of mast cell activation J. Leukoc. Biol., February 1, 2006; 79(2): 363 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Jenmalm, H. Cherwinski, E. P. Bowman, J. H. Phillips, and J. D. Sedgwick Regulation of Myeloid Cell Function through the CD200 Receptor J. Immunol., January 1, 2006; 176(1): 191 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bachelet, A. Munitz, A. Moretta, L. Moretta, and F. Levi-Schaffer The Inhibitory Receptor IRp60 (CD300a) Is Expressed and Functional on Human Mast Cells J. Immunol., December 15, 2005; 175(12): 7989 - 7995. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Fallarino, C. Orabona, C. Vacca, R. Bianchi, S. Gizzi, C. Asselin-Paturel, M. C. Fioretti, G. Trinchieri, U. Grohmann, and P. Puccetti Ligand and cytokine dependence of the immunosuppressive pathway of tryptophan catabolism in plasmacytoid dendritic cells Int. Immunol., November 1, 2005; 17(11): 1429 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Shiratori, M. Yamaguchi, M. Suzukawa, K. Yamamoto, L. L. Lanier, T. Saito, and H. Arase Down-Regulation of Basophil Function by Human CD200 and Human Herpesvirus-8 CD200 J. Immunol., October 1, 2005; 175(7): 4441 - 4449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hatherley, H. M. Cherwinski, M. Moshref, and A. N. Barclay Recombinant CD200 Protein Does Not Bind Activating Proteins Closely Related to CD200 Receptor J. Immunol., August 15, 2005; 175(4): 2469 - 2474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Cameron, J. W. Barrett, L. Liu, A. R. Lucas, and G. McFadden Myxoma Virus M141R Expresses a Viral CD200 (vOX-2) That Is Responsible for Down-Regulation of Macrophage and T-Cell Activation In Vivo J. Virol., May 15, 2005; 79(10): 6052 - 6067. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
