Abstract
ENGAGEMENT of the T-cell receptor (TCR) with cognate ligands provokes different outcomes depending on the developmental stage of the T cell and on the properties of the ligand. In immature thymocytes TCR stimulation may result in maturation (positive selection) or death (negative selection), whereas in mature T cells it may induce proliferation, death or unresponsiveness1–5. To investigate the different signals involved in these processes, we have analysed the role of the MAP kinase (MAPK) cascade, which is required for growth-factor-stimulated replication and for differentiation in other cell types6–9, by expressing a catalytically inactive form of MAPK kinase (MEK-1) in thymocytes, thereby blocking MAPK activation. We find that positive selection of these cells is inhibited but that negative selection and TCR-induced proliferation are unaffected. Our results indicate that the intracellular signals regulating lineage commitment in T cells parallel those in photo-receptor cell specification in Drosophila10 and vulval cell differentiation in Caenorhabditis elegans11 suggesting that general rules for cell-type specification could apply among all metazoans.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
von Boehmer, H. Cell 76, 219–228 (1994).
Nossal, G. J. V. Cell 76, 229–240 (1994).
Janeway, C. A. Jr & Bottomly, K. Cell 76, 275–286 (1994).
Kang, S. M. et al. Science 257, 1134–1138 (1992).
Rocha, B. & von Boehmer, H. Science 251, 1225–1228 (1991).
Ahn, N. G., Seger, R. & Krebs, E. G. Curr. Opin. Cell Biol. 4, 992–999 (1992).
Pages, G. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8319–8323 (1993).
Seger, R. et al. J. biol. Chem. 269, 25699–25709 (1994).
Cowley, S., Paterson, H., Kemp, P. & Marshall, C. J. Cell 77, 841–852 (1994).
Dickson, B. & Hafen, E. Curr. Opin. genet. Dev. 4, 64–70 (1994).
Eisenmann, D. M. & Kim, S. K. Curr. Opin. genet. Dev. 4, 508–516 (1994).
Wildin, R. S. et al. J. exp. Med. 173, 383–393 (1991).
Egerton, M., Shortman, K. & Scollay, R. Int. Immun. 2, 501–507 (1990).
Swat, W., Dessing, M., Baron, A., Kisielow, P. & von Boehmer, H. Eur. J. Immun. 22, 2367–2372 (1992).
Teh, H. S. et al. Nature 335, 229–233 (1988).
Kisielow, P., Bluthmann, H., Staerz, U. D., Steinmetz, M. & von Boehmer, H. Nature 333, 742–746 (1988).
von Boehmer, H., Kirberg, J. & Rocha, B. J. exp. Med. 174, 1001–1008 (1991).
Rayter, S. I., Woodrow, M., Lucas, S. C., Cantrell, D. A. & Downward, J. EMBO J. 11, 4549–4556 (1992).
Swan, K. A. et al. EMBO J. 14, 276–285 (1995).
Su, B. et al. Cell 77, 727–736 (1994).
Brunner, D. et al. Nature 370, 386–389 (1994).
O'Neill, E. M., Rebay, I., Tjian, R. & Rubin, G. M. Cell 78, 137–147 (1994).
Chan, A. C., Desai, D. M. & Weiss, A. A. Rev. Immun. 12, 555–592 (1994).
Downward, J., Graves, J. D., Warne, P. H., Rayter, S. & Cantrell, D. A. Nature 346, 719–723 (1990).
Avruch, J., Zhang, Z. & Kyriakis, J. M. Trends biochem. Sci. 19, 279–283 (1994).
Seger, R. et al. J. biol. Chem. 267, 25628–25631 (1992).
Chaffin, K. E. et al. EMBO J. 9, 3821–3829 (1990).
Garvin, A. M. et al. Int. Immun. 2, 173–180 (1990).
Appleby, M. W. et al. Cell 70, 751–763 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Alberola-lla, J., Forbush, K., Seger, R. et al. Selective requirement for MAP kinase activation in thymocyte differentiation. Nature 373, 620–623 (1995). https://doi.org/10.1038/373620a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/373620a0
This article is cited by
-
Targeting polo-like kinase 1 suppresses essential functions of alloreactive T cells
Immunologic Research (2016)
-
N-glycosylation bidirectionally extends the boundaries of thymocyte positive selection by decoupling Lck from Ca2+ signaling
Nature Immunology (2014)
-
Generation and purification of highly specific antibodies for detecting post-translationally modified proteins in vivo
Nature Protocols (2014)
-
The clinical development of MEK inhibitors
Nature Reviews Clinical Oncology (2014)
-
Shb deficient mice display an augmented TH2 response in peripheral CD4+ T cells
BMC Immunology (2011)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.