Interleukin-2 (IL-2) induces tyrosine kinase-dependent translocation of active raf-1 from the IL-2 receptor into the cytosol.
Stimulation of the interleukin-2 (IL-2) receptor results in phosphorylation and activation of cytosolic Raf-1 serine/threonine kinase. Herein, we report that enzymatically active Raf-1 is physically associated with the IL-2 receptor beta chain (p75) in T-cell blasts. Following stimulation with IL-2, Raf-1 dissociates from the IL-2 receptor complex and translocates to the cytosol. Genistein, a protein tyrosine kinase inhibitor, prevents the dissociation of enzymatically active Raf-1 from the ligand-stimulated IL-2 receptor complex. These data favor a model of IL-2 receptor activation in which an IL-2-activated protein tyrosine kinase phosphorylates the IL-2 receptor and/or receptor-bound Raf-1. Following tyrosine phosphorylation, enzymatically active Raf-1 dissociates from the IL-2 receptor and translocates into the cytosol.
Maslinski
W
W
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts.
Remillard
B
B
Tsudo
M
M
Strom
T B
TB
D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D008715:Methionine / Q000097:blood; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011494:Protein Kinases / Q000097:blood*; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000097:blood*; D019908:Proto-Oncogene Proteins c-raf; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D008715:Methionine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D019908:Proto-Oncogene Proteins c-raf