Signal transduction by lymphocyte antigen receptors.
Despite the differences in the antigens that they recognize and in the effector functions they carry out, B and T lymphocytes utilize remarkably similar signal transduction components to initiate responses. They both use oligomeric receptors that contain distinct recognition and signal transduction subunits. Antigen receptors on both cells interact with at least two distinct families of PTKs via common sequence motifs, ARAMs, in the cytoplasmic tails of their invariant chains, which have likely evolved from a common evolutionary precursor. Coreceptors appear to serve to increase the sensitivity of both of these receptor systems through events that influence ligand binding and signal transduction. The critical role of tyrosine phosphorylation of downstream signaling components, such as phospholipase C, is the net result of changes in the balance of the action of antigen receptor-regulated PTKs and PTPases. The identification of downstream effectors, including calcineurin and Ras, that regulate cellular responses, such as lymphokine gene expression, promises the future possibility of connecting the complex pathway from the plasma membrane to the nucleus in lymphocytes. Insight gained from studies of the signaling pathways downstream of TCR and BCR stimulation is likely to contribute significantly to future understanding of mechanisms responsible for lymphocyte differentiation and for the discrimination of self from nonself in developing and mature cells.
Weiss
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Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.
Littman
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D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D019703:Calcineurin; D002118:Calcium / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000502:physiology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015290:Second Messenger Systems; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
D002148:Calmodulin-Binding Proteins; D046911:Macromolecular Substances; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D017493:Leukocyte Common Antigens; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D002118:Calcium