Regulation of PtdIns-3-kinase and the guanine nucleotide binding proteins p21ras during signal transduction by the T cell antigen receptor and the interleukin-2 receptor.
The T cell antigen receptor (TCR) and the interleukin-2 receptor (IL-2R) are important receptors in haematopoiesis since they control the activation and growth of T lymphocytes, respectively. The term T cell activation refers to the events that occur as T cells progress from the G0 to the G1 phase of the cell cycle and is characterised by the production of a wide range of cytokines and other immunomodulators crucial for the growth and development of other haematopoietic cells. Activation also induces the T cells to express on their cell surface high affinity receptors for various cytokines which enable the T cell to respond to the different cytokines generated during an immune response. One well characterised event that occurs when mature T cells are activated is the production of the cytokine IL-2 and the acquisition by the T cell of high affinity IL-2 receptors. Interaction between IL-2 and its cellular receptor than direct T cell growth. One notable difference between TCR and IL-2R signal transduction is that the TCR regulates intracellular calcium and stimulates protein kinase C whereas the IL-2 receptor does not. The present review focuses on TCR and IL-2R regulation of two common intracellular signalling pathways: the regulation of a PtdIns-3-kinase and the activation of the guanine nucleotide binding proteins p21ras. The aim is to illustrate differences in the mechanisms that couple the TCR and IL-2R to these two signalling pathways and attempt to explain the apparent discrepancy of TCR and IL-2R regulation of shared signal transduction pathways even though these receptors mediate quite distinct biological responses.
Cantrell
D A
DA
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, UK.
Izquierdo
M
M
Reif
K
K
Woodrow
M
M
D000818:Animals; D006801:Humans; D008213:Lymphocyte Activation; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology
D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)