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Signal transduction by interleukin 2 in human T cells: Activation of tyrosine and ribosomal S6 kinases and cell‐cycle regulatory genes
Author(s) -
Sawami Hiroyasu,
Terada Naohiro,
Franklin Richard A.,
Okawa Hiroji,
Uchiyama Takashi,
Lucas Joseph J.,
Gelfand Erwin W.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041510218
Subject(s) - biology , ribosomal s6 kinase , kinase , signal transduction , microbiology and biotechnology , receptor tyrosine kinase , tyrosine kinase , p70 s6 kinase 1 , pi3k/akt/mtor pathway
The early events of signal transduction associated with interleukin‐2 (IL‐2) binding to its receptor were examined using a human IL‐2 dependent T‐cell line, Kit225. Cell cycle analysis showed that 90% of Kit225 cells were in the G 0 /G 1 phase after a 72‐hr incubation in the absence of exogenous IL‐2. At this point, stimulation of the cells with IL‐2 resulted in the rapid initiation of RNA and DNA synthesis by 9 and 20 hr, respectively. Within 5 min after addition of IL‐2, rapid activation of tyrosine and ribosomal S6 kinases was detected. Addition of IL‐2 also increased mRNA levels for c‐ fos , c‐ myc , IL‐2 receptor α, and IL‐2 receptor β chain. These events increased in the absence of detectable changes in free cytosolic [Ca 2+ ] i , inositol phosphate metabolism, or the activity of several kinases including cAMP‐dependent protein kinase, Ca 2+ /calmodulin‐dependent protein kinase, or protein kinase C. These findings demonstrate that the signals triggered by IL‐2 binding to its receptors are quickly transduced into the nucleus with increased mRNA transcription of activation‐associated genes. Furthermore, the data indicate that tyrosine and ribosomal S6 kinases may be important for IL‐2‐induced cell growth. © 1992 Wiley‐Liss, Inc.