| First Author | Lee MK | Year | 2007 |
| Journal | EMBO J | Volume | 26 |
| Issue | 17 | Pages | 3957-67 |
| PubMed ID | 17673906 | Mgi Jnum | J:200409 |
| Mgi Id | MGI:5508603 | Doi | 10.1038/sj.emboj.7601818 |
| Citation | Lee MK, et al. (2007) TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J 26(17):3957-67 |
| abstractText | Erk1/Erk2 MAP kinases are key regulators of cell behaviour and their activation is generally associated with tyrosine kinase signalling. However, TGF-beta stimulation also activates Erk MAP kinases through an undefined mechanism, albeit to a much lower level than receptor tyrosine kinase stimulation. We report that upon TGF-beta stimulation, the activated TGF-beta type I receptor (TbetaRI) recruits and directly phosphorylates ShcA proteins on tyrosine and serine. This dual phosphorylation results from an intrinsic TbetaRI tyrosine kinase activity that complements its well-defined serine-threonine kinase function. TGF-beta-induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well-characterised pathway linking receptor tyrosine kinases with Erk MAP kinases. We also found that TbetaRI is tyrosine phosphorylated in response to TGF-beta. Thus, TbetaRI, like the TGF-beta type II receptor, is a dual-specificity kinase. Recruitment of tyrosine kinase signalling pathways may account for aspects of TGF-beta biology that are independent of Smad signalling. |
