Role of insulin receptor substrate-2 in interleukin-9-dependent proliferation

Interleukin-9 (IL-9) stimulation results in JAK, STAT and IRS1/2 phosphoryl ation. The role of IRS adaptor proteins in IL-9 signaling is not clear. We show that IL-9 induces IRS2 phosphorylation and association with phosphatid ylinositol-3 kinase (PI 3-K) p85 subunit in TS1 cells and BaF/9R cells. whi ch proliferate upon IL-9 stimulation. We observed a PI 3-K-dependent phosph orylation of protein kinase B (PKB) in TS1 cells, but not in BaF/9R, nor in other IL-9-dependent cell lines. Finally, 32D cells that were transfected with the IL-9 receptor but lack IRS expression survived in the presence of IL-9. Ectopic IRS1 expression allowed for IL-9-Induced proliferation, in th e absence of significant PKB phosphorylation. (C) 2000 Federation of Europe an Biochemical Societies. Published by Elsevier Science B.V. All rights res erved.