Interleukin 2-induced activation of Ras requires two domains of interleukin 2 receptor beta subunit, the essential region for growth stimulation and Lck-binding domain.
Interleukin 2 (IL-2) can stimulate the proliferation of various kinds of T-cell lines. The receptor for IL-2 is composed of at least two subunits (alpha and beta), of which beta subunit plays the major role in transducing growth signals into the cells. A nonreceptor-type tyrosine kinase, Lck, is associated with IL-2 receptor beta subunit, and the binding of IL-2 to its receptor induces the activation of Lck. On the other hand, it has been shown that stimulation of T-cells with IL-2 causes rapid activation of Ras protein. In this paper, we describe that both of the two regions in IL-2 receptor beta subunit, the indispensable region for the induction of cell growth (serine-rich region) and the binding region of Lck protein (acidic region), are required for the activation of Ras. These two regions are also required for tyrosine phosphorylation of an 85-kDa cellular protein (p85) and the accumulation of fos and jun mRNAs. This observation suggests also that the activation of a receptor-associated tyrosine kinase in response to IL-2-stimulation is primarily responsible for subsequent activation of the pathway through Ras to Fos and Jun.
Satoh
T
T
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304.
Minami
Y
Y
Kono
T
T
Yamada
K
K
Kawahara
A
A
Taniguchi
T
T
Kaziro
Y
Y
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D016762:Genes, fos; D016758:Genes, jun; D011905:Genes, ras / Q000187:drug effects*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
D007376:Interleukin-2; D046911:Macromolecular Substances; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D013936:Thymidine