STAT ACTIVATION BY EPIDERMAL GROWTH-FACTOR (EGF) AND AMPHIREGULIN - REQUIREMENT FOR THE EGF RECEPTOR KINASE BUT NOT FOR TYROSINE PHOSPHORYLATION SITES OR JAK1

The epidermal growth factor (EGF) receptor activates several signaling cascades in response to the ligands EGF and amphiregulin (AR). One of these signaling events involves the tyrosine phosphorylation of STATs (signal transducers and activators of transcription), a process belie ved to require the activation of a tyrosine kinase of the JAK family, In this report we demonstrate that EGF- and AR-induced STAT activation requires the intrinsic kinase activity of the receptor but not the pr esence of Jak1. We show that both wild type (WT) and truncated EGF rec eptors lacking all autophosphorylation sites activate STAT 1, 3, and 5 in response to either EGF or AR. Furthermore, relative to cells expre ssing WT receptor, ligand-induced tyrosine phosphorylation of the STAT s was enhanced in cells expressing only the truncated receptor, These results provide the first evidence that (i) EGF receptor-mediated STAT activation occurs in a Jak1-independent manner, (ii) the intrinsic ty rosine kinase activity of the receptor is essential for STAT activatio n, and (iii) tyrosine phosphorylation sites within the EGF receptor ar e not required for STAT activation.