| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Immunobiology Working Group, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111;
Division of Immunology, The Netherlands Cancer Institute, Amersterdam, The Netherlands; and
Rosetta Inpharmatics, Kirkland, WA 98034
Progression of immature CD4-CD8-
thymocytes beyond the 
-selection checkpoint to the
CD4+CD8+ stage requires activation of the
pre-TCR complex; however, few of the DNA-binding proteins that serve as
molecular effectors of those pre-TCR signals have been identified. We
demonstrate in this study that members of the early growth response
(Egr) family of transcription factors are critical effectors of the
signals that promote this developmental transition. Specifically, the
induction of three Egr family members (Egr1, 2, and 3) correlates with
pre-TCR activation and development of
CD4-CD8- thymocytes beyond the -selection
checkpoint. Enforced expression of each of these Egr factors is able to
bypass the block in thymocyte development associated with defective
pre-TCR function. However, Egr family members may play somewhat
distinct roles in promoting thymocyte development, because there are
differences in the genes modulated by enforced expression of particular
Egr factors. Finally, interfering with Egr function using
dominant-negative proteins disrupts thymocyte development from the
CD4-CD8- to the
CD4+CD8+ stage. Taken together, these data
demonstrate that the Egr proteins play an essential role in executing
the differentiation program initiated by pre-TCR
signaling.
This article has been cited by other articles:
|
|
 |
|
  N. J. Rowbotham, A. L. Hager-Theodorides, A. L. Furmanski, S. E. Ross, S. V. Outram, J. T. Dessens, and T. Crompton Sonic hedgehog negatively regulates pre-TCR-induced differentiation by a Gli2-dependent mechanism Blood, May 21, 2009; 113(21): 5144 - 5156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xu, A. Sharma, D. L. Wiest, and J. M. Sen Pre-TCR-Induced {beta}-Catenin Facilitates Traversal through {beta}-Selection J. Immunol., January 15, 2009; 182(2): 751 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xu, A. Sharma, M. Z. Hossain, D. L. Wiest, and J. M. Sen Sustained Expression of Pre-TCR Induced {beta}-Catenin in Post-{beta}-Selection Thymocytes Blocks T Cell Development J. Immunol., January 15, 2009; 182(2): 759 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. H. Lauritsen, S. Kurella, S.-Y. Lee, J. M. Lefebvre, M. Rhodes, J. Alberola-Ila, and D. L. Wiest Egr2 Is Required for Bcl-2 Induction during Positive Selection J. Immunol., December 1, 2008; 181(11): 7778 - 7785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gururajan, A. Simmons, T. Dasu, B. T. Spear, C. Calulot, D. A. Robertson, D. L. Wiest, J. G. Monroe, and S. Bondada Early Growth Response Genes Regulate B Cell Development, Proliferation, and Immune Response J. Immunol., October 1, 2008; 181(7): 4590 - 4602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kawazu, G. Yamamoto, M. Yoshimi, K. Yamamoto, T. Asai, M. Ichikawa, S. Seo, M. Nakagawa, S. Chiba, M. Kurokawa, et al. Expression Profiling of Immature Thymocytes Revealed a Novel Homeobox Gene That Regulates Double-Negative Thymocyte Development J. Immunol., October 15, 2007; 179(8): 5335 - 5345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Koltsova, M. Ciofani, R. Benezra, T. Miyazaki, N. Clipstone, J. C. Zuniga-Pflucker, and D. L. Wiest Early Growth Response 1 and NF-ATc1 Act in Concert to Promote Thymocyte Development beyond the beta-Selection Checkpoint J. Immunol., October 1, 2007; 179(7): 4694 - 4703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Carter, J. M. Lefebvre, D. L. Wiest, and W. G. Tourtellotte Redundant Role for Early Growth Response Transcriptional Regulators in Thymocyte Differentiation and Survival J. Immunol., June 1, 2007; 178(11): 6796 - 6805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mao, E. G. Tili, M. Dose, M. C. Haks, S. E. Bear, I. Maroulakou, K. Horie, G. A. Gaitanaris, V. Fidanza, T. Ludwig, et al. Unequal Contribution of Akt Isoforms in the Double-Negative to Double-Positive Thymocyte Transition J. Immunol., May 1, 2007; 178(9): 5443 - 5453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Roberts, J. P. H. Lauritsen, M. Cooney, R. E. Parrott, E. O. Sajaroff, C. M. Win, M. D. Keller, J. H. Carpenter, J. Carabana, M. S. Krangel, et al. T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3{zeta} subunit of the T-cell antigen receptor complex Blood, April 15, 2007; 109(8): 3198 - 3206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Carter and W. G. Tourtellotte Early Growth Response Transcriptional Regulators Are Dispensable for Macrophage Differentiation J. Immunol., March 1, 2007; 178(5): 3038 - 3047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ke, M. Gururajan, A. Kumar, A. Simmons, L. Turcios, R. L. Chelvarajan, D. M. Cohen, D. L. Wiest, J. G. Monroe, and S. Bondada The Role of MAPKs in B Cell Receptor-induced Down-regulation of Egr-1 in Immature B Lymphoma Cells J. Biol. Chem., December 29, 2006; 281(52): 39806 - 39818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Patra, T. Drewes, S. Engelmann, S. Chuvpilo, H. Kishi, T. Hunig, E. Serfling, and U. H. Bommhardt PKB Rescues Calcineurin/NFAT-Induced Arrest of Rag Expression and Pre-T Cell Differentiation J. Immunol., October 1, 2006; 177(7): 4567 - 4576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Munoz, D. Alfaro, J. Garcia-Ceca, L. M. Alonso-C, E. Jimenez, and A. Zapata Thymic Alterations in EphA4-Deficient Mice J. Immunol., July 15, 2006; 177(2): 804 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Lefebvre, M. C. Haks, M. O. Carleton, M. Rhodes, G. Sinnathamby, M. C. Simon, L. C. Eisenlohr, L. A. Garrett-Sinha, and D. L. Wiest Enforced Expression of Spi-B Reverses T Lineage Commitment and Blocks {beta}-Selection J. Immunol., May 15, 2005; 174(10): 6184 - 6194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Williams, P. W. Bland, A. C. Phillips, S. Turner, T. Brooklyn, G. Shaya, R. D. Spicer, and C. S. J. Probert Intestinal {alpha}{beta} T Cells Differentiate and Rearrange Antigen Receptor Genes In Situ in the Human Infant J. Immunol., December 15, 2004; 173(12): 7190 - 7199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Balmelle, N. Zamarreno, M. S. Krangel, and C. Hernandez-Munain Developmental Activation of the TCR {alpha} Enhancer Requires Functional Collaboration among Proteins Bound Inside and Outside the Core Enhancer J. Immunol., October 15, 2004; 173(8): 5054 - 5063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Singh, J. Svaren, J. Grayson, and M. Suresh CD8 T Cell Responses to Lymphocytic Choriomeningitis Virus in Early Growth Response Gene 1-Deficient Mice J. Immunol., September 15, 2004; 173(6): 3855 - 3862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Grady, S. M. Mason, J. Stephen, J. C. Zuniga-Pflucker, and A. M. Michie Cyclic Adenosine 5'-Monophosphate Response Element Binding Protein Plays a Central Role in Mediating Proliferation and Differentiation Downstream of the Pre-TCR Complex in Developing Thymocytes J. Immunol., August 1, 2004; 173(3): 1802 - 1810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Lee, K. Hanspers, C. S. Barker, A. P. Korn, and J. M. McCune Gene expression profiles during human CD4+ T cell differentiation Int. Immunol., August 1, 2004; 16(8): 1109 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tabrizifard, A. Olaru, J. Plotkin, M. Fallahi-Sichani, F. Livak, and H. T. Petrie Analysis of Transcription Factor Expression during Discrete Stages of Postnatal Thymocyte Differentiation J. Immunol., July 15, 2004; 173(2): 1094 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xi and G. J. Kersh Sustained Early Growth Response Gene 3 Expression Inhibits the Survival of CD4/CD8 Double-Positive Thymocytes J. Immunol., July 1, 2004; 173(1): 340 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xi and G. J. Kersh Early Growth Response Gene 3 Regulates Thymocyte Proliferation during the Transition from CD4-CD8- to CD4+CD8+1 J. Immunol., January 15, 2004; 172(2): 964 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. de Mestre, L. M. Khachigian, F. S. Santiago, M. A. Staykova, and M. D. Hulett Regulation of Inducible Heparanase Gene Transcription in Activated T Cells by Early Growth Response 1 J. Biol. Chem., December 12, 2003; 278(50): 50377 - 50385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Keeton, K. D. Bortoff, W. L. Bennett, J. L. Franklin, D. Y. Venable, and J. L. Messina Insulin-Regulated Expression of Egr-1 and Krox20: Dependence on ERK1/2 and Interaction with p38 and PI3-Kinase Pathways Endocrinology, December 1, 2003; 144(12): 5402 - 5410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D. Ragione, V. Cucciolla, V. Criniti, S. Indaco, A. Borriello, and V. Zappia p21Cip1 Gene Expression Is Modulated by Egr1: A NOVEL REGULATORY MECHANISM INVOLVED IN THE RESVERATROL ANTIPROLIFERATIVE EFFECT J. Biol. Chem., June 20, 2003; 278(26): 23360 - 23368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Haks, S. M. Belkowski, M. Ciofani, M. Rhodes, J. M. Lefebvre, S. Trop, P. Hugo, J. C. Zuniga-Pflucker, and D. L. Wiest Low Activation Threshold As a Mechanism for Ligand-Independent Signaling in Pre-T Cells J. Immunol., March 15, 2003; 170(6): 2853 - 2861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xi and G. J. Kersh Induction of the Early Growth Response Gene 1 Promoter by TCR Agonists and Partial Agonists: Ligand Potency Is Related to Sustained Phosphorylation of Extracellular Signal-Related Kinase Substrates J. Immunol., January 1, 2003; 170(1): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bettini, H. Xi, J. Milbrandt, and G. J. Kersh Thymocyte Development in Early Growth Response Gene 1-Deficient Mice J. Immunol., August 15, 2002; 169(4): 1713 - 1720. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
