CDB25:0003951 MIF — 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

Secreted and O-GlcNAcylated MIF binds to the human EGF receptor and inhibits its activation.

Nature cell biology, 2015; PubMed, Homo sapiens MIF — Homo sapiens EGFR

ABSTRACT: Activation of epidermal growth factor receptor (EGFR), which occurs in many types of tumour, promotes tumour progression. However, no extracellular antagonist of human EGFR has been identified. We found that human macrophage migration inhibitory factor (MIF) is O-GlcNAcylated at Ser 112/Thr 113 at its carboxy terminus. The naturally secreted and O-GlcNAcylated MIF binds to EGFR, thereby inhibiting the binding of EGF to EGFR and EGF-induced EGFR activation, phosphorylation of ERK and c-Jun, cell invasion, proliferation and brain tumour formation. Activation of EGFR through mutation or its ligand binding enhances the secretion of MMP13, which degrades extracellular MIF, and results in abrogation of the negative regulation of MIF on EGFR. The finding that EGFR activation downregulates its antagonist in the tumour microenvironment represents an important feedforward mechanism for human tumour cells to enhance EGFR signalling and promote tumorigenesis.

Basic Information on MIF

Ligand Name: macrophage migration inhibitory factor

Other Symbols: GLIF, GIF

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: MIF

GeneCards: MIF

HGNC Gene Group: unknown

Functional Annotations for MIF

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 MIF

MIF — CD74 ・ MIF — CXCR2 ・ MIF — CXCR4 ・ MIF — ACKR3

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