Src-dependent phosphorylation of the EGF receptor Tyr-845 mediates Stat-p21waf1 pathway in A431 cells.

Background: Cell surface receptor for the epidermal growth factor (EGFR) and cytoplasmic tyrosine kinase c-Src co-operate in several cellular functions such as proliferation and apoptosis. Our previous studies have shown that ectopic expression of the adaptor protein p52shc or p66shc, but not p46shc, and EGF stimulation lead to the activation of c-Src that is accompanied by phosphorylation of signal transducers and activators of transcription (Stat) in A431 cells.

Results: Here, we show that by using A431 cells as a model system, expression of p52shc, or cell stimulation with EGF or H2O2 leads to phosphorylation of EGFR on Tyr 845 that is located to the activation segment of the catalytic domain.

Inhibition and activation of c-Src: the head and tail of a coin.

Protein-tyrosine kinases (PTKs) play pivotal roles in many cell systems. The Src family kinases (SFKs) are the most characterized PTKs shown to be coupled with various cell surface receptors. However, their mode of activation and regulating partners are largely unknown.

Adaptor protein Shc is an isoform-specific direct activator of the tyrosine kinase c-Src.

The activity of c-Src protein-tyrosine kinase is up-regulated under a number of receptor signaling pathways. However, the activation mechanism of c-Src under physiological conditions has remained unclear. We show here that the Shc adaptor protein is a novel direct activator of c-Src in epidermal growth factor receptor signaling in A431 human epidermoid carcinoma cells.