Role of insulin receptor substrate-2 in interleukin-9-dependent proliferation.
Interleukin-9 (IL-9) stimulation results in JAK, STAT and IRS1/2 phosphorylation. The role of IRS adaptor proteins in IL-9 signaling is not clear. We show that IL-9 induces IRS2 phosphorylation and association with phosphatidylinositol-3 kinase (PI 3-K) p85 subunit in TS1 cells and BaF/9R cells, which proliferate upon IL-9 stimulation. We observed a PI 3-K-dependent phosphorylation 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 the absence of significant PKB phosphorylation.
Demoulin
J B
JB
Ludwig Institute for Cancer Research and Experimental Medicine Unit, Université Catholique de Louvain, Brussels, Belgium. jean-baptiste.demoulin@bru.licr.org
Grasso
L
L
Atkins
J M
JM
Stevens
M
M
Louahed
J
J
Levitt
R C
RC
Nicolaides
N C
NC
Renauld
J C
JC
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D016906:Interleukin-9 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt
D016326:Extracellular Matrix Proteins; D055504:Insulin Receptor Substrate Proteins; D016906:Interleukin-9; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C490607:ECM1 protein, human; C094556:Ecm1 protein, mouse; C526297:IRS2 protein, human; C526298:Irs2 protein, mouse