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Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine- rich
region within IL-2 receptor beta c chain
M Adachi, M Sekiya, T Torigoe, S Takayama, JC Reed, T Miyazaki, Y Minami, T Taniguchi and K Imai
First Department of Internal Medicine, Sapporo Medical University School of
Medicine, Japan.
BAG-1 is a Bci-2-binding protein which functions in protection from
apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-
mediated upregulation of BAG-1 expression. In hematopoietic cell line
BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c
chain is sufficient to confer proliferation and cell survival responses to
IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically
induced by IL-2. The IL-2-mediated induction of BAG-1 expression required
the activation of tyrosine kinase(s) and was sensitive to rapamycin as the
induction of bcl-2 expression was. Analysis of the transfectants which
express mutant IL-2R beta c chains or mutant Janus family protein tyrosine
kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1
gene expression required the serinerich region within the IL-2R beta c
chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1
gene expression thus highly resembles that for bcl-2 gene expression,
strongly suggesting that their induction shares the same signaling pathway.
In addition, deletion of the serine-rich region led to loss of
IL-2-mediated protection from apoptotic cell death. Taken together, these
studies demonstrate that the serine-rich region of the IL-2R beta c chain
mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby
contributing to suppression of apoptosis.
Volume 88,
Issue 11,
pp. 4118-4123,
12/01/1996
Copyright © 1996 by The American Society of Hematology
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