CDB25:0003264 CCN2 — 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

Connective tissue growth factor is a new ligand of epidermal growth factor receptor.

Journal of molecular cell biology, 2013; PubMed, Homo sapiens CCN2 — Homo sapiens EGFR

ABSTRACT: Chronic kidney disease is reaching epidemic proportions worldwide and there is no effective treatment. Connective tissue growth factor (CCN2) has been suggested as a risk biomarker and a potential therapeutic target for renal diseases, but its specific receptor has not been identified. Epidermal growth factor receptor (EGFR) participates in kidney damage, but whether CCN2 activates the EGFR pathway is unknown. Here, we show that CCN2 is a novel EGFR ligand. CCN2 binding to EGFR extracellular domain was demonstrated by surface plasmon resonance. CCN2 contains four distinct structural modules. The carboxyl-terminal module (CCN2(IV)) showed a clear interaction with soluble EGFR, suggesting that EGFR-binding site is located in this module. Injection of CCN2(IV) in mice increased EGFR phosphorylation in the kidney, mainly in tubular epithelial cells. EGFR kinase inhibition decreased CCN2(IV)-induced renal changes (ERK activation and inflammation). Studies in cultured tubular epithelial cells showed that CCN2(IV) binds to EGFR leading to ERK activation and proinflammatory factors overexpression. CCN2 interacts with the neurotrophin receptor TrkA, and EGFR/TrkA receptor crosstalk was found in response to CCN2(IV) stimulation. Moreover, endogenous CCN2 blockade inhibited TGF-β-induced EGFR activation. These findings indicate that CCN2 is a novel EGFR ligand that contributes to renal damage through EGFR signalling.

Basic Information on CCN2

Ligand Name: cellular communication network factor 2

Other Symbols: CTGF, IGFBP8

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: CCN2

GeneCards: CCN2

HGNC Gene Group: Cellular communication network factors

Functional Annotations for CCN2

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 CCN2

CCN2 — ITGA5 ・ CCN2 — ITGAM ・ CCN2 — ITGB2 ・ CCN2 — LRP1 ・ CCN2 — LRP6 ・ CCN2 — NTRK1 ・ CCN2 — FGFR2 ・ CCN2 — IGF2R ・ CCN2 — FGFR1 ・ CCN2 — FGFR3 ・ CCN2 — ITGB1 ・ CCN2 — TGFBR1

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 ・ EPGN — EGFR ・ EREG — EGFR ・ HBEGF — EGFR ・ L1CAM — EGFR ・ SPINK1 — EGFR ・ TGFA — EGFR ・ TNC — EGFR ・ ANG — EGFR ・ GPNMB — EGFR ・ LRIG1 — EGFR ・ LRIG2 — EGFR ・ MIF — EGFR ・ NRG3 — EGFR ・ PLA2G2A — EGFR ・ S100A4 — EGFR ・ ST6GAL1 — EGFR ・ WNT9A — EGFR