p21ras initiates Rac-1 but not phosphatidyl inositol 3 kinase/PKB, mediated signaling pathways in T lymphocytes (original) (raw)

Oncogene volume 17, pages 1731–1738 (1998)Cite this article

Abstract

p21ras is activated by the T cell antigen receptor (TCR) and then co-ordinates important signaling pathways for T lymphocyte activation. Effector pathways for this guanine nucleotide binding protein in T cells are mediated by the serine/threonine kinase Raf-1 and the Ras-related GTPase Rac-1. In fibroblasts, an important effector for the Ras oncogene is Phosphatidylinositol 3-kinase (PtdIns 3-kinase). Activation of this lipid kinase is able to induce critical Rac-1 signaling pathways and can couple p21ras to cell survival mechanisms via the serine/threonine kinase Akt/PKB. The role of PtdIns 3-kinase in Ras signaling in T cells has not been explored. In the present study, we examined the ability of PtdIns 3-kinase to initiate the Rac-1 signaling pathways important for T cell activation. We also examined the possibility that Akt/PKB is regulated by Ras signaling pathways in T lymphocytes. The results show that Ras can initiate a Rac-1 mediated pathway that regulates the transcriptional function of AP-1 complexes. PtdIns 3-kinase signals cannot mimic p21ras and induce the Rac mediated responses of AP-1 transcriptional activation. Moreover, neither TCR or Ras activation of AP-1 is dependent on PtdIns 3-kinase. PKB is activated in response to triggering of the T cell antigen receptor; PtdIns 3-kinase activity is both required and sufficient for this TCR response. In contrast, p21ras signals are unable to induce Akt/PKB activity in T cell nor is Ras function required for Akt/PKB activation in response to the TCR. The present data thus highlight that PtdIns 3-kinase and Akt/PKB are not universal Ras effector molecules. Ras can initiate Rac-1 regulated signaling pathways in the context of T cell antigen receptor function independently of PtdIns 3-kinase activity.

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Author notes

  1. Elisabeth Genot & Sarah Beach
    Present address: Department of Immunology, Imperial College, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
  2. Karin Reif
    Present address: Department of Microbiology and Immunology, 513 Parnassus, Box 0414, Rm HSE301, University of California, San Francisco, 94143–0414, California, USA

Authors and Affiliations

  1. Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK
    Doreen Cantrell
  2. Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT
    Ijsbrand Kramer

Authors

  1. Elisabeth Genot
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  2. Karin Reif
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  3. Sarah Beach
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  4. Ijsbrand Kramer
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  5. Doreen Cantrell
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Genot, E., Reif, K., Beach, S. et al. p21ras initiates Rac-1 but not phosphatidyl inositol 3 kinase/PKB, mediated signaling pathways in T lymphocytes.Oncogene 17, 1731–1738 (1998). https://doi.org/10.1038/sj.onc.1202101

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