Asset Details
Do you wish to reserve the book?
Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr 701 phosphorylation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr 701 phosphorylation
Do you wish to request the book?
Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr 701 phosphorylation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr 701 phosphorylation
2020
Overview
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 Thr
phosphorylation, leading to AKT de-phosphorylation, via PP2A Ser/Thr phosphatases. Furthermore, the immunophilin Cyclophilin A plays a crucial role in this pathway, acting as a negative modulator of AKT de-phosphorylation, possibly by competing with Ser/Thr phosphatases for binding to AKT. Altogether, our data show that Ab recognizing ERBB2 extracellular domain function as receptor agonists, promoting ERBB2 homodimer activation, leading to an anti-proliferative signaling. Thus, the ultimate outcome of ERBB2 activity might depend on the dimerization status: pro-oncogenic in the hetero-, and anti-oncogenic in the homo-dimeric form.
Subject
/ Cell Proliferation - physiology
/ Cell Transformation, Neoplastic - metabolism
/ Cytostatic Agents - metabolism
/ Extracellular Signal-Regulated MAP Kinases
/ Humans
/ Phosphorylation - physiology
/ Proto-Oncogene Proteins c-akt - metabolism
/ Receptor Protein-Tyrosine Kinases - metabolism
