The SH3 domain of PLC-gl has been known to be responsible for the mitogenu effect of PLC-gl and also to be implicated in the control of the lipase activity of the PLC-gl protein. However, little is known about the putative effector pro teins that bind to the PLC-gl SH3 domain. We provide evidence that SOSl, one of the activators of p21 Ras, binds to the SH3 domain of PLC-gl. SOSl co-precipitated with the GST-fused SH3 domain of PLC-gl in vitro. The inter action between SOSl and PLC-gl is mediated by direct physical interaction. Moreover, the C-terminal proline-rich domain of SOSl is involved in the inter action with the PLC-gl SH3 domain. PLC-gl could be co-immunoprecipitated with SOSl antibody. The association between SOSl and SH3 domain of PLC-gl was not influenced by either the activation of the EGF receptor or v-Src-induced transformation in vitro. However, in vivo association between SOSl and PLCgl was slightly potenciated by the activation of EGF-receptor. Furthermore, in transient expression studies with COS-7 cells, we characterized the association between PLC-gl and SOSl in vivo. We could demonstrate that the SH3 domain of PLC-gl is absolutely required for the association with SOSl in vivo. SOSl over-expression in COS-7 cells inhibited EGF-induced Pi-turnover and EGFinduced tyrosyl phosphorylation of PLC-gl. Based on all these observations together, we propose that SOSl may act as a possible regulator in a PLC-gl mediated signaling pathway.
|Publication status||Published - 1998|
ASJC Scopus subject areas
- Molecular Biology