Interaction of the c-fes proto-oncogene product with the interleukin-4 receptor.
Interleukin-4 (IL-4) regulates proliferation and differentiation of a variety of hematopoietic cell lineages through binding to the IL-4 receptor (IL-4R). Recently, we have demonstrated that IL-4 induces tyrosine phosphorylation of several proteins including the IL-4R and also induces association of phosphatidylinositol-3 kinase with the IL-4R. Since IL-4 induces tyrosine phosphorylation, we speculated that some tyrosine kinase may associate with the IL-4R. In this study, we demonstrate that IL-4 induces tyrosine phosphorylation of a protein closely related to, or identical to the c-fes protooncogene-encoded protein tyrosine kinase (FES). Furthermore, tyrosine phosphorylated FES or the closely related protein is found associated with the IL-4R. We also demonstrate that FES associates with the IL-4R in COS7 cells transfected with cDNA expression plasmids encoding these two proteins and in transfected COS7 cells IL-4 augments association of FES with the IL-4R and tyrosine phosphorylation of both FES and the IL-4R. Through a deletion analysis of the IL-4R we have identified a putative FES-binding site in the cytoplasmic domain of the IL-4R.
Izuhara
K
K
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304-1104.
Feldman
R A
RA
Greer
P
P
Harada
N
N
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051578:Proto-Oncogene Proteins c-fes; D011519:Proto-Oncogenes; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes