Regulation and function of p21ras in T lymphocytes.
T cell activation is triggered by antigen stimulation and is characterized by the production of a wide range of cytokines and other immunomodulators crucial for the growth and development of other haemopoietic cells. Activation also induces the T cells to express, on their cell surface, receptors that enable the T cell to respond to the various cytokines generated during an immune response. One well characterized event that occurs when mature T cells are activated is the production of the cytokine IL2 and the acquisition by the T cell of IL2 receptors. Interaction between IL2 and its cellular receptor then directs T cell growth. Expression of the IL2 gene in T cells is regulated by signalling pathways that originate from the T cell antigen receptor complex (TCR). This review discusses the role of p21ras in these events. The TCR regulates the activity of p21ras, and a range of experiments have shown that p21ras couples the TCR to an intracellular kinase cascade involving the serine/threonine kinase Raf-1 and the MAP kinase ERK2. Analysis of more distal receptor signals shows that p21ras controls a signalling pathway that cooperates with a calcium/calcineurin controlled signalling system to stimulate the transcriptional factor NFAT and hence the IL2 gene. These studies identify p21ras as a critical signalling molecule in immune cells.
Pastor
M I
MI
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London.
Woodrow
M
M
Cantrell
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000276:immunology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D006150:Guanine Nucleotides; D007376:Interleukin-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011494:Protein Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D002118:Calcium