CDB15:0001483 TNC — EGFR

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

Title

Journal:; Year Published:

Abstract

Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor.

The Journal of cell biology, 2001; PubMed, Homo sapiens TNC — Mus Musculus Egfr

ABSTRACT: Signaling through growth factor receptors controls such diverse cell functions as proliferation, migration, and differentiation. A critical question has been how the activation of these receptors is regulated. Most, if not all, of the known ligands for these receptors are soluble factors. However, as matrix components are highly tissue-specific and change during development and pathology, it has been suggested that select growth factor receptors might be stimulated by binding to matrix components. Herein, we describe a new class of ligand for the epidermal growth factor (EGF) receptor (EGFR) found within the EGF-like repeats of tenascin-C, an antiadhesive matrix component present during organogenesis, development, and wound repair. Select EGF-like repeats of tenascin-C elicited mitogenesis and EGFR autophosphorylation in an EGFR-dependent manner. Micromolar concentrations of EGF-like repeats induced EGFR autophosphorylation and activated extracellular signal-regulated, mitogen-activated protein kinase to levels comparable to those induced by subsaturating levels of known EGFR ligands. EGFR-dependent adhesion was noted when the ligands were tethered to inert beads, simulating the physiologically relevant presentation of tenascin-C as hexabrachion, and suggesting an increase in avidity similar to that seen for integrin ligands upon surface binding. Specific binding to EGFR was further established by immunofluorescence detection of EGF-like repeats bound to cells and cross-linking of EGFR with the repeats. Both of these interactions were abolished upon competition by EGF and enhanced by dimerization of the EGF-like repeat. Such low affinity behavior would be expected for a matrix-"tethered" ligand; i.e., a ligand which acts from the matrix, presented continuously to cell surface EGF receptors, because it can neither diffuse away nor be internalized and degraded. These data identify a new class of "insoluble" growth factor ligands and a novel mode of activation for growth factor receptors.

Basic Information on TNC

Ligand Name: tenascin C

Other Symbols: HXB, DFNA56, TN, MGC167029

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: TNC

GeneCards: TNC

HGNC Gene Group: Fibrinogen C domain containing, Fibronectin type III domain containing

Functional Annotations for TNC

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 TNC

TNC — CNTN1 ・ TNC — ITGA2 ・ TNC — ITGA7 ・ TNC — ITGA8 ・ TNC — ITGA9 ・ TNC — ITGAV ・ TNC — ITGB1 ・ TNC — PTPRB ・ TNC — PTPRZ1 ・ TNC — ITGB3 ・ TNC — CNTN2 ・ TNC — FN1 ・ TNC — ITGB6 ・ TNC — TLR4

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 ・ ANG — EGFR ・ CCN2 — EGFR ・ GPNMB — EGFR ・ LRIG1 — EGFR ・ LRIG2 — EGFR ・ MIF — EGFR ・ NRG3 — EGFR ・ PLA2G2A — EGFR ・ S100A4 — EGFR ・ ST6GAL1 — EGFR ・ WNT9A — EGFR