CDB15:0000535 EPGN — EGFR

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics.

Cell, 2017; PubMed, Homo sapiens EPGN — Homo sapiens EGFR

ABSTRACT: Epidermal growth factor receptor (EGFR) regulates many crucial cellular programs, with seven different activating ligands shaping cell signaling in distinct ways. Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. As a consequence, EREG or EPGN induce less stable EGFR dimers than EGF-making them partial agonists of EGFR dimerization. Unexpectedly, this weakened dimerization elicits more sustained EGFR signaling than seen with EGF, provoking responses in breast cancer cells associated with differentiation rather than proliferation. Our results reveal how responses to different EGFR ligands are defined by receptor dimerization strength and signaling dynamics. These findings have broad implications for understanding receptor tyrosine kinase (RTK) signaling specificity. Our results also suggest parallels between partial and/or biased agonism in RTKs and G-protein-coupled receptors, as well as new therapeutic opportunities for correcting RTK signaling output.

Basic Information on EPGN

Ligand Name: epithelial mitogen

Other Symbols: EPG, PRO9904, ALGV3072

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: EPGN

GeneCards: EPGN

HGNC Gene Group: unknown

Functional Annotations for EPGN

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for EPGN

Basic Information on EGFR

Receptor Name: epidermal growth factor receptor

Other Symbols: ERBB, ERBB1, ERRP

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: EGFR

GeneCards: EGFR

HGNC Gene Group: Receptor kinases

Functional Annotations for EGFR

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for EGFR

AMH — EGFR ・ AREG — EGFR ・ BTC — EGFR ・ DCN — EGFR ・ EFEMP1 — EGFR ・ EGF — EGFR ・ EREG — EGFR ・ HBEGF — EGFR ・ L1CAM — EGFR ・ SPINK1 — EGFR ・ TGFA — EGFR ・ TNC — EGFR ・ ANG — EGFR ・ CCN2 — EGFR ・ GPNMB — EGFR ・ LRIG1 — EGFR ・ LRIG2 — EGFR ・ MIF — EGFR ・ NRG3 — EGFR ・ PLA2G2A — EGFR ・ S100A4 — EGFR ・ ST6GAL1 — EGFR ・ WNT9A — EGFR