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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.[1]


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