Evidence for a critical role for the cytoplasmic region of the interleukin 2 (IL-2) receptor gamma chain in IL-2, IL-4, and IL-7 signalling.
The high-affinity interleukin 2 receptor (IL-2R) consists of at least three distinct subunits: the IL-2R alpha chain (IL-2R alpha), beta chain (IL-2R beta), and gamma chain (IL-2R gamma). It has been shown that the cytoplasmic region of IL-2R beta, but not of IL-2R alpha, is essential for IL-2 signalling to the cell interior. In the present study, we examined the functional role of the IL-2R gamma cytoplasmic region in the IL-3-dependent mouse hematopoietic cell line BAF-B03, which expresses the endogenous IL-2R alpha and IL-2R gamma, or its subline F7, which additionally expresses human IL-2R beta cDNA. We show that overexpression of a mutant IL-2R gamma, lacking all but 7 amino acids of its cytoplasmic region, results in the selective inhibition of IL-2-induced c-fos gene activation and cellular proliferation in F7 cells. When two chimeric receptor molecules in which the cytoplasmic regions of IL-2R beta and IL-2R gamma had been swapped with each other (IL-2R beta/gamma and IL-2R gamma/beta) were coexpressed in BAF-B03, the cells responded to IL-2. These results indicate the critical importance of the IL-2-induced functional cooperation of the two cytoplasmic regions. Finally, we provide evidence that the IL-2R gamma cytoplasmic region is also critical for the IL-4 and IL-7-induced growth signal transduction in BAF-B03.
Institute for Molecular and Cellular Biology, Osaka University, Japan.
A
A
Kawahara
Y
Y
Minami
T
T
Taniguchi
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D016762:Genes, fos; D016259:Genes, myc; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000502:physiology; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; D011975:Receptors, Mitogen / Q000502:physiology*; D015398:Signal Transduction; D015533:Transcriptional Activation
D007376:Interleukin-2; D015851:Interleukin-7; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; D011975:Receptors, Mitogen; D015847:Interleukin-4