The IL-2 receptor complex: its structure, function, and target genes.
Proliferation of T lymphocytes is triggered by the interaction of IL-2 with its specific receptor following T lymphocyte activation. The receptor for IL-2 consists of at least three distinct subunits, the alpha chain (IL-2R alpha), the beta chain (IL-2R beta), and the gamma chain (IL-2R gamma). Although the role of IL-2R gamma in IL-2 signalling remains unclear, IL-2R beta is the subunit critical for receptor-mediated signalling. Because IL-2R beta lacks any apparent catalytic motifs, IL-2R beta may be physically or functionally coupled to other signalling molecules. Structure-function studies of IL-2R beta have revealed that at least two distinct cytoplasmic regions of IL-2R beta are involved in IL-2-induced cellular signalling. The "serine-rich" region of IL-2R beta was identified as a region critical for IL-2-induced mitotic signalling from experiments in which IL-2R beta mutant cDNAs lacking a particular cytoplasmic region or regions were expressed in an IL-3-dependent mouse pro-B cell line (BAF-B03). Meanwhile, another cytoplasmic region of IL-2R beta, the "acidic" region, is responsible for its physical association with an src-family protein tyrosine kinase (PTK), p56lck and is critical for activating the p56lck PTK following IL-2 stimulation. It is now evident that IL-2R beta is linked to at least two intracellular signalling pathways that mediate nuclear proto-oncogene induction. One pathway is linked to tyrosine phosphorylation events, mediated by a src-family protein tyrosine kinase (PTK), and that pathway leads to the induction of the c-fos, c-jun, and other genes of this family. Another pathway leads to c-myc gene induction by an as yet unknown mechanism. We discuss the complex signalling machinery that links the cell surface receptor to the nuclear events.
Minami
Y
Y
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kono
T
T
Miyazaki
T
T
Taniguchi
T
T
D000818:Animals; D006801:Humans; D015394:Molecular Structure; D005810:Multigene Family; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D011971:Receptors, Immunologic / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases