Negative regulation of T cell receptor signals.
T cells undergo clonal expansion upon encountering cognate antigen in peripheral lymphoid tissues. They require signals through both the T cell receptor and the costimulatory receptor CD28 for this process to occur. In the absence of CD28 stimulation, T cell receptor signals are repressed by the ubiquitin ligase Cbl-b, which negatively regulates the activity of the downstream effectors PI3Kp85 and Vav1. CD28 signals overcome this repression, at least in part, by ubiquitinating and degrading Cbl-b itself. CD28 signals induce clustering of cell-surface receptors, cell division and optimal interleukin-2 production. The Cbl-b/CD28 regulatory axis has profound implications for pathological conditions ranging from autoimmunity to cancer.
Rangachari
Manu
M
University of Toronto, Ontario, Canada.
Penninger
Josef M
JM
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D051966:Phospholipase C gamma; D011493:Protein Kinase C / Q000502:physiology; D000074121:Protein Kinase C-theta; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050721:Proto-Oncogene Proteins c-cbl; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000502:physiology
D018106:CD28 Antigens; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; C067419:CBL protein, human