INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-7, AND INTERLEUKIN-15 STIMULATE TYROSINE PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 AND SUBSTRATE-2 IN T-CELLS - POTENTIAL ROLE OF JAK KINASES
Ja. Johnston et al., INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-7, AND INTERLEUKIN-15 STIMULATE TYROSINE PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 AND SUBSTRATE-2 IN T-CELLS - POTENTIAL ROLE OF JAK KINASES, The Journal of biological chemistry, 270(48), 1995, pp. 28527-28530
The signaling molecules insulin receptor substrate (IRS)-1 and the new
ly described IRS-2 (4PS) molecule are major insulin and interleukin 4
(IL-4)-dependent phosphoproteins. We report here that IL-2, IL-7, and
IL-15, as well as IL-4, rapidly stimulate the tyrosine phosphorylation
of IRS-1 and IRS-2 in human peripheral blood T cells, NK cells, and i
n lymphoid cell lines. In addition, we show that the Janus kinases, JA
K1 and JAK3, associate with IRS-1 and IRS-2 in T cells. Coexpression s
tudies demonstrate that these kinases can tyrosine-phosphorylate IRS-2
, suggesting a possible mechanism by which cytokine receptors may indu
ce the tyrosine phosphorylation of IRS-1 and IRS-2. We further demonst
rate that the p85 subunit of phosphoinositol 3-kinase associates with
IRS-1 in response to IL-2 and IL-4 in T cells. Therefore, these data i
ndicate that IRS-1 and IRS-2 may have important roles in T lymphocyte
activation not only in response to IL-4, but also in response to IL-2,
IL-7, and IL-15.