PKCζ als neues Effektormolekül des EGF Rezeptors : Aktivierung durch Protein-Protein Interaktion und Phosphorylierung an Threonin 410 und Tyrosin 417
The activity and function of protein kinase C (PKC) isoforms can be regulated by tyrosine phosphorylation. In this study we identified the tyrosine phosphorylation of protein kinase C zeta (PKCζ) as a novel effector mechanism mediated by epidermal growth factor receptor (EGFR). Physical association between PKCζ and EGFR in COS-7 cells and in the breast cancer cell line MCF-7 as well as colocalization of PKCζ with EGFR at the plasma membrane in response to EGFR stimulation has been demonstrated. The catalytic activation of PKCζ within the EGFR signalling complex involves not only phosphoinositide-dependent kinase 1 (PDK1)-mediated phosphorylation of threonine 410 at the activation loop, but also requires phosphorylation of the neighboring tyrosine 417. The EGFR-induced tyrosine phosphorylation of PKCζ as an integral part of its catalytic activation contributes to the proliferative and pro-survival functions of PKCζ in EGFR signalling pathway.