CDB15:0000609 FGF2 — FGFR2

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

Identification of residues important both for primary receptor binding and specificity in fibroblast growth factor-7.

The Journal of biological chemistry, 2000; PubMed, Homo sapiens FGF2 — Homo sapiens FGFR2

ABSTRACT: Fibroblast growth factors (FGFs) mediate a multitude of physiological and pathological processes by activating a family of tyrosine kinase receptors (FGFRs). Each FGFR binds to a unique subset of FGFs and ligand binding specificity is essential in regulating FGF activity. FGF-7 recognizes one FGFR isoform known as the FGFR2 IIIb isoform or keratinocyte growth factor receptor (KGFR), whereas FGF-2 binds well to FGFR1, FGFR2, and FGFR4 but interacts poorly with KGFR. Previously, mutations in FGF-2 identified a set of residues that are important for high affinity receptor binding, known as the primary receptor-binding site. FGF-7 contains this primary site as well as a region that restricts interaction with FGFR1. The sequences that confer on FGF-7 its specific binding to KGFR have not been identified. By utilizing domain swapping and site-directed mutagenesis we have found that the loop connecting the beta4-beta5 strands of FGF-7 contributes to high affinity receptor binding and is critical for KGFR recognition. Replacement of this loop with the homologous loop from FGF-2 dramatically reduced both the affinity of FGF-7 for KGFR and its biological potency but did not result in the ability to bind FGFR1. Point mutations in residues comprising this loop of FGF-7 reduced both binding affinity and biological potency. The reciprocal loop replacement mutant (FGF2-L4/7) retained FGF-2 like affinity for FGFR1 and for KGFR. Our results show that topologically similar regions in these two FGFs have different roles in regulating receptor binding specificity and suggest that specificity may require the concerted action of distinct regions of an FGF.

Basic Information on FGF2

Ligand Name: fibroblast growth factor 2

Other Symbols: FGFB

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: FGF2

GeneCards: FGF2

HGNC Gene Group: Fibroblast growth factor family, Receptor ligands

Functional Annotations for FGF2

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 FGF2

FGF2 — CD44 ・ FGF2 — FGFR1 ・ FGF2 — FGFR3 ・ FGF2 — FGFR4 ・ FGF2 — FGFRL1 ・ FGF2 — GPC4 ・ FGF2 — NRP1 ・ FGF2 — SDC1 ・ FGF2 — SDC2 ・ FGF2 — SDC3 ・ FGF2 — SDC4 ・ FGF2 — CSPG4 ・ FGF2 — ITGAV ・ FGF2 — ITGB3 ・ FGF2 — LYVE1 ・ FGF2 — TGFBR3

Basic Information on FGFR2

Receptor Name: fibroblast growth factor receptor 2

Other Symbols: KGFR, BEK, CFD1, JWS, CEK3, TK14, TK25, ECT1, K-SAM, CD332

Receptor Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: FGFR2

GeneCards: FGFR2

HGNC Gene Group: Receptor kinases, CD molecules, Immunoglobulin superfamily domain containing

Functional Annotations for FGFR2

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 FGFR2

FGF10 — FGFR2 ・ FGF16 — FGFR2 ・ FGF17 — FGFR2 ・ FGF18 — FGFR2 ・ FGF19 — FGFR2 ・ FGF1 — FGFR2 ・ FGF21 — FGFR2 ・ FGF22 — FGFR2 ・ FGF23 — FGFR2 ・ FGF3 — FGFR2 ・ FGF4 — FGFR2 ・ FGF5 — FGFR2 ・ FGF6 — FGFR2 ・ FGF7 — FGFR2 ・ FGF8 — FGFR2 ・ FGF9 — FGFR2 ・ NCAM1 — FGFR2 ・ PF4 — FGFR2 ・ CCN2 — FGFR2 ・ FGF20 — FGFR2 ・ FAM3B — FGFR2