Regulation and function of p21ras in T lymphocytes

Abstract

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.