Interleukin-4 activates two distinct pathways of phosphatidylinositol-3 kinase in the same cells.
We have recently demonstrated that c-fes protooncogene product (FES), or a FES-related protein, associates with the interleukin-4 receptor alpha chain (IL-4R alpha) and phosphatidylinositol-3 (PI3) kinase in mouse T cell lines; however, others have demonstrated that PI3 kinase associates with IL-4R alpha through tyrosine phosphorylated insulin receptor substrate (IRS)-2 in other cell types. In order to examine whether IL-4 activates these two distinct PI3 kinase pathways in the same cells, we analyzed association of PI3 kinase with IRS-2, and tyrosine phosphorylation of IRS-2, in a mouse pro-B cell line, Ba/F3, and a mouse mast cell line, MC9. In both cell lines, IL-4 induced tyrosine phosphorylation of IRS-2, association of PI3 kinase with IRS-2, and FES or a FES-related protein. These results indicate that IL-4 activates two distinct PI3 kinase pathways in the same cells. We further identified the critical region in the cytoplasmic domain of IL-4R alpha required for tyrosine phosphorylation of IRS-2.
Izuhara
K
K
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304-1104, USA.
Harada
N
N
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D018123:Receptors, Interleukin / Q000378:metabolism; D019948:Receptors, Interleukin-4; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)