THE IL-2 RECEPTOR COMPLEX - ITS STRUCTURE, FUNCTION, AND TARGET GENES

被引:397
作者
MINAMI, Y
KONO, T
MIYAZAKI, T
TANIGUCHI, T
机构
关键词
IL-2 RECEPTOR BETA-CHAIN (IL-2R-BETA); SIGNAL TRANSDUCTION; CELLULAR PROLIFERATION; TYROSINE KINASE ACTIVATION; NUCLEAR PROTOONCOGENE INDUCTION;
D O I
10.1146/annurev.iy.11.040193.001333
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-2Ralpha), the beta chain (IL-2Rbeta), and the gamma chain (IL-2Rgamma). Although the role of IL-2Rgamma in IL-2 signalling remains unclear, IL-2Rbeta is the subunit critical for receptor-mediated signalling. Because IL-2Rbeta lacks any apparent catalytic motifs, IL-2Rbeta may be physically or functionally coupled to other signalling molecules. Structure-function studies of IL-2Rbeta have revealed that at least two distinct cytoplasmic regions of IL-2Rbeta are involved in IL-2-induced cellular signalling. The ''serine-rich'' region of IL-2Rbeta was identified as a region critical for IL-2-induced mitotic signalling from experiments in which IL-2Rbeta 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-2Rbeta, 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-2Rbeta 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.
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页码:245 / 268
页数:24
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