Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase.
We have previously demonstrated that interleukin-4 (IL-4) induces tyrosine phosphorylation of a protein closely related or identical to the c-fes proto-oncogene product (FES) and association of this protein with the IL-4 receptor alpha chain (IL-4R alpha). IL-4 is known to induce association of phosphatidylinositol-3 (PI3) kinase with the IL-4R alpha. Since FES contains the consensus motifs for PI3 kinase binding, we tested the possibility that FES may associate with PI3 kinase upon IL-4 stimulation. We demonstrate herein that IL-4 stimulation induced rapid association of FES or a related protein with PI3 kinase in mouse T-cell lines. We also show an association of human FES (hFES) with the src homology 2 (SH2) domain of PI3 kinase in a COS7 cell expression system. The in vitro PI3 kinase assay using COS7 cells suggested that hFES partly contributes to the association between the hIL-4R alpha and PI3 kinase. We have further identified the important region in the cytoplasmic domain of the hIL-4R alpha for association of tyrosine-phosphorylated hFES with the hIL-4R alpha and SH2 domain of PI3 kinase using a COS7 cell expression system. These results suggest that FES or a related protein/PI3 kinase pathway may play a role in the pleiotropic effects of IL-4.
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA, USA.
K
K
Izuhara
R A
RA
Feldman
P
P
Greer
N
N
Harada
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D015847:Interleukin-4 / Q000494:pharmacology*; D046911:Macromolecular Substances; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051578:Proto-Oncogene Proteins c-fes; D018123:Receptors, Interleukin / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D018909:src Homology Domains
D015703:Antigens, CD; D015847:Interleukin-4; D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051578:Proto-Oncogene Proteins c-fes; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; C000715470:MAS1 protein, human; C496646:Fes protein, mouse