Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr⁷⁰¹ phosphorylation.

ABSTRACT: ERBB2 is a ligand-less tyrosine kinase receptor expressed at very low levels in normal tissues; when overexpressed, it is involved in malignant transformation and tumorigenesis in several carcinomas. In cancer cells, ERBB2 represents the preferred partner of other members of the ERBB receptor family, leading to stronger oncogenic signals, by promoting both ERK and AKT activation. The identification of the specific signaling downstream of ERBB2 has been impaired by the lack of a ligand and of an efficient way to selectively activate the receptor. In this paper, we found that antibodies (Abs) targeting different epitopes on the ERBB2 extracellular domain foster the activation of ERBB2 homodimers, and surprisingly induce a unique cytostatic signaling cascade promoting an ERK-dependent ERBB2 T

SUBMITTER: Gaviraghi M 

PROVIDER: S-EPMC7547737 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature