Interaction of Shc with the zeta chain of the T cell receptor upon T cell activation.
The shc oncogene product is tyrosine-phosphorylated by Src family kinases and after its phosphorylation interacts with the adapter protein Grb2 (growth factor receptor-bound protein 2). In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Because several Src family kinases participate in T cell activation and Shc functions upstream of Ras, the role of Shc in T cell signaling was examined. Shc was phosphorylated on tyrosine after activation through the T cell receptor (TCR), and subsequently interacted with Grb2 and mSOS. The Src homology region 2 (SH2) domain of Shc directly interacted with the tyrosine-phosphorylated zeta chain of the TCR. Thus, Shc may couple TCR activation to the Ras signaling pathway.
Ravichandran
K S
KS
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Lee
K K
KK
Songyang
Z
Z
Cantley
L C
LC
Burn
P
P
Burakoff
S J
SJ
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D020664:Son of Sevenless Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D008565:Membrane Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D020664:Son of Sevenless Proteins; C054979:antigen T cell receptor, zeta chain; D014443:Tyrosine; D066246:ErbB Receptors; D019204:GTP-Binding Proteins