| First Author | Harmer SL | Year | 1997 |
| Journal | Mol Cell Biol | Volume | 17 |
| Issue | 7 | Pages | 4087-95 |
| PubMed ID | 9199344 | Mgi Jnum | J:326666 |
| Mgi Id | MGI:7316616 | Doi | 10.1128/MCB.17.7.4087 |
| Citation | Harmer SL, et al. (1997) Shc contains two Grb2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes. Mol Cell Biol 17(7):4087-95 |
| abstractText | Cross-linking of the B-cell antigen receptor (BCR) induces tyrosine phosphorylation of Shc, which is believed to lead to the activation of Ras. Previous work has shown that tyrosine-phosphorylated Shc forms complexes with another adapter protein, Grb2, and the Ras guanine nucleotide exchange factor SOS. Here, we demonstrate that phosphorylation of Shc by the hematopoietic cell-specific tyrosine kinase Syk induces binding of Grb2 to Shc, suggesting that Syk phosphorylates Shc in stimulated B cells. Surprisingly, Syk-phosphorylated Shc possesses two Grb2 binding sites rather than the one site that has been previously reported. Both of these sites are required for efficient formation of Shc-Grb2-SOS complexes in vitro and in vivo. We suggest that two Grb2 proteins anchored by a single Shc protein bind simultaneously to one SOS molecule, resulting in a complex that is more stable than a complex containing only a single Grb2 protein bound to one SOS molecule. This model is consistent with our observation that BCR stimulation greatly increases the amount of SOS associated with Grb2. |
