CDB15:0000425 DCN — 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

Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope.

The Journal of biological chemistry, 2002; PubMed, Homo sapiens DCN — Homo sapiens EGFR

ABSTRACT: Decorin, a small leucine-rich proteoglycan, is a key regulator of tumor growth by acting as an antagonist of the epidermal growth factor receptor (EGFR) tyrosine kinase. To search for cell surface receptors interacting with decorin, we generated a decorin/alkaline phosphatase chimeric protein and used it to screen a cDNA library by expression cloning. We identified two strongly reactive clones that encoded either the full-length EGFR or its ectodomain. A physiologically relevant interaction between decorin and EGFR was confirmed in the yeast two-hybrid system and further validated by experiments using EGF/EGFR interaction and transient cell transfection assays. Using a panel of deletion mutants, decorin binding was mapped to a narrow region of the EGFR within its ligand-binding L2 domain. Moreover, the central leucine-rich repeat 6 of decorin was required for interaction with the EGFR. Site-directed mutagenesis of the EGFR L2 domain showed that a cluster of residues, His(394)-Ile(402), was essential for both decorin and EGF binding. In contrast, K465, previously shown to be cross-linked to epidermal growth factor (EGF), was required for EGF but not for decorin binding. Thus, decorin binds to a discrete region of the EGFR, partially overlapping with but distinct from the EGF-binding domain. These findings could lead to the generation of protein mimetics capable of suppressing EGFR function.

Decorin is a biological ligand for the epidermal growth factor receptor.

The Journal of biological chemistry, 1999; PubMed, Homo sapiens DCN — Homo sapiens EGFR

ABSTRACT: Ectopic expression of decorin induces profound cytostatic effects in transformed cells with diverse histogenetic backgrounds. The mechanism of action has only recently begun to be elucidated. Exogenous decorin activates the epidermal growth factor (EGF) receptor, thereby triggering a signaling cascade that leads to phosphorylation of mitogen-activated protein (MAP) kinase, induction of p21, and growth suppression. In this study we demonstrate a direct interaction of decorin with the EGF receptor. Binding of decorin induces dimerization of the EGF receptor and rapid and sustained phosphorylation of MAP kinase in squamous carcinoma cells. In a cell-free system, decorin induces autophosphorylation of purified EGF receptor by activating the receptor tyrosine kinase and can also act as a substrate for the EGF receptor kinase itself. Using radioligand binding assays we show that both immobilized and soluble decorin bind to the EGF receptor ectodomain or to purified EGF receptor. The binding is mediated by the protein core and has relatively low affinity (Kd approximately 87 nM). Thus, decorin should be considered as a novel biological ligand for the EGF receptor, an interaction that could regulate cell growth during remodeling and cancer growth.

Basic Information on DCN

Ligand Name: decorin

Other Symbols: DSPG2, SLRR1B

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: DCN

GeneCards: DCN

HGNC Gene Group: Proteoglycans

Functional Annotations for DCN

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 DCN

DCN — ERBB4 ・ DCN — MET ・ DCN — TLR2 ・ DCN — TLR4 ・ DCN — KDR

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 ・ EFEMP1 — EGFR ・ EGF — EGFR ・ EPGN — 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