The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation.
Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) stimulates Src family kinases, tyrosine phosphorylation of several proteins, conversion of Ras to its active GTP-bound form, and eventually c-fos, c-jun, and c-myc induction. The IL-2R beta chain plays a crucial role in IL-2R signaling. Within the cytoplasmic domain of the beta chain, a region essential for mitogenesis and another involved in binding the Src family kinase Lck have been defined. The beta chain itself is tyrosine-phosphorylated upon IL-2 stimulation. Since the adapter protein Shc acts upstream of Ras and is involved in T cell receptor-mediated Ras activation, we examined the role of Shc in IL-2 signaling. Shc was found to be tyrosine-phosphorylated upon IL-2 stimulation in CTLL-20 cells. After its phosphorylation, Shc interacted with another adapter protein, Grb2, and, via Grb2, with the Ras GTP/GDP exchange factor mSOS. After IL-2 stimulation, Shc also associated with the IL-2R beta chain. Thus, during IL-2 signaling, the interaction of Shc with the IL-2R beta chain and its simultaneous association with Grb2 and mSOS may couple IL-2R stimulation to Ras signaling.
Ravichandran
K S
KS
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Burakoff
S J
SJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D051380:GRB2 Adaptor Protein; D019204:GTP-Binding Proteins / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D011485:Protein Binding; D011506:Proteins / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D011519:Proto-Oncogenes; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D007376:Interleukin-2; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2; D019204:GTP-Binding Proteins