Shc regulates epidermal growth factor-induced activation of the JNK signaling pathway

Two adaptor molecules, Grb2 and Shc, have been implicated in the extracellu lar signal-regulated kinase (ERK) activation by receptor tyrosine kinases s uch as the epidermal growth factor receptor (EGFR). Here we show that the E GF-mediated ERK activation is abolished by loss of Grb2, whereas this respo nse is not affected by loss of Shc. Conversely, the EGF-mediated c-Jun N-te rminal kinase (JNK) activation is dependent on Shc, but not Grb2. These fin dings strongly support distinct roles for Grb2 and Shc in controlling ERK a nd JNK activation after EGF stimulation.