The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3.
Ligation of the T cell receptor for antigen (TCR) and/or costimulatory receptor CD28 results in rapid activation of phosphoinositide-3 kinase (PI-3 kinase). It remains unclear, however, precisely how this activation occurs and also how the newly generated phospholipid products trigger the various events associated with T cell activation. Here we discuss the current understanding of how PI-3 kinase is activated by the TCR and CD28 and what roles its products play in T cell activation. We also review recent advances in understanding the function of Akt in particular, especially its role in CD28 costimulation. Several functional targets of Akt are discussed in this regard: inducible transcription, cell survival, glucose metabolism, and the cellular translational machinery. These pathways have been associated with TCR/CD28 costimulation, and they have also been implicated as targets of Akt.
Kane
Lawrence P
LP
Department of Medicine, The Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Weiss
Arthur
A
D018106:CD28 Antigens / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D018448:Models, Immunological; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism
D018106:CD28 Antigens; D018797:Cell Cycle Proteins; D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; C494918:AKT1 protein, human