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Downregulation of ERBB2:ERBB3 signaling

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-1358803

PubChem

R-HSA-1358803

Description

Level of plasma membrane ERBB3 is regulated by E3 ubiquitin ligase RNF41 (also known as NRDP1), which binds and ubiquitinates both inactive and activated ERBB3, targeting it for degradation (Cao et al. 2007). RNF41 is subject to self-ubiquitination which keeps its levels low when ERBB3 is not stimulated, and preserves ERBB3 expression on the cell surface (Qiu et al. 2002). Self-ubiquitination of RNF41 is reversible, through the action of ubiquitin protease USP8, an enzyme stabilized by AKT-mediated phosphorylation. Therefore, activation of AKT by ERBB2:ERBB3 signaling leads to phosphorylation of USP8 (Cao et al. 2007), which increases level of RNF41 through deubiquitination, and results in degradation of activated ERBB3 (Cao et al. 2007) - a negative feedback loop of ERBB3 signaling. Downregulation of EGFR and ERBB4 signaling is explained in pathways Signaling by EGFR and Signaling by ERBB4.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 9** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O14511	Pro-neuregulin-2, membrane-bound isoform	NRG2 NTAK	view
P04626	Receptor tyrosine-protein kinase erbB-2	ERBB2 HER2 MLN19 NEU NGL	view
P31749	RAC-alpha serine/threonine-protein kinase	AKT1 PKB RAC	view
P31751	RAC-beta serine/threonine-protein kinase	AKT2	view
P40818	Ubiquitin carboxyl-terminal hydrolase 8	KIAA0055 UBPY USP8	view
P62979	Ubiquitin-ribosomal protein eS31 fusion protein	RPS27A UBA80 UBCEP1	view
P62987	Ubiquitin-ribosomal protein eL40 fusion protein	UBA52 UBCEP2	view
Q02297	Pro-neuregulin-1, membrane-bound isoform	GGF HGL HRGA NDF NRG1 SMDF	view
Q9Y243	RAC-gamma serine/threonine-protein kinase	AKT3 PKBG	view

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