CDB25:0003624 FGF2 — ITGB3

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

The integrin-binding defective FGF2 mutants potently suppress FGF2 signalling and angiogenesis.

Bioscience reports, 2017; PubMed, Homo sapiens FGF2 — Homo sapiens ITGB3

ABSTRACT: We recently found that integrin αvβ3 binds to fibroblast growth factor (FGF)-αvβ31 (FGF1), and that the integrin-binding defective FGF1 mutant (Arg-50 to glutamic acid, R50E) is defective in signalling and antagonistic to FGF1 signalling. R50E suppressed angiogenesis and tumour growth, suggesting that R50E has potential as a therapeutic. However, FGF1 is unstable, and we had to express R50E in cancer cells for xenograft study, since injected R50E may rapidly disappear from circulation. We studied if we can develop antagonist of more stable FGF2. FGF2 is widely involved in important biological processes such as stem cell proliferation and angiogenesis. Previous studies found that FGF2 bound to αvβ3 and antagonists to αvβ3 suppressed FGF2-induced angiogenesis. However, it is unclear how FGF2 interacts with integrins. Here, we describe that substituting Lys-119/Arg-120 and Lys-125 residues in the predicted integrin-binding interface of FGF2 to glutamic acid (the K119E/R120E and K125E mutations) effectively reduced integrin binding to FGF2. These FGF2 mutants were defective in signalling functions (ERK1/2 activation and DNA synthesis) in NIH3T3 cells. Notably they suppressed, FGF2 signalling induced by WT FGF2 in endothelial cells, suggesting that the FGF2 mutants are antagonists. The FGF2 mutants effectively suppressed tube formation in vitro, sprouting in aorta ring assays ex vivo and angiogenesis in vivo The positions of amino acids critical for integrin binding are different between FGF1 and FGF2, suggesting that they do not interact with integrins in the same manner. The newly developed FGF2 mutants have potential as anti-angiogenic agents and useful tools for studying the role of integrins in FGF2 signalling.

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 — FGFR2 ・ FGF2 — FGFR3 ・ FGF2 — FGFR4 ・ FGF2 — FGFRL1 ・ FGF2 — GPC4 ・ FGF2 — NRP1 ・ FGF2 — SDC1 ・ FGF2 — SDC2 ・ FGF2 — SDC3 ・ FGF2 — SDC4 ・ FGF2 — CSPG4 ・ FGF2 — ITGAV ・ FGF2 — LYVE1 ・ FGF2 — TGFBR3

Basic Information on ITGB3

Receptor Name: integrin subunit beta 3

Other Symbols: GP3A, CD61, GPIIIa

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: ITGB3

GeneCards: ITGB3

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGB3

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 ITGB3

ADAM15 — ITGB3 ・ ADAM23 — ITGB3 ・ ANGPTL3 — ITGB3 ・ CCN1 — ITGB3 ・ FBLN2 — ITGB3 ・ FBN1 — ITGB3 ・ FGA — ITGB3 ・ FN1 — ITGB3 ・ ICAM4 — ITGB3 ・ MFGE8 — ITGB3 ・ NID1 — ITGB3 ・ TGM2 — ITGB3 ・ THBS1 — ITGB3 ・ VTN — ITGB3 ・ COMP — ITGB3 ・ CX3CL1 — ITGB3 ・ CXCL12 — ITGB3 ・ EDIL3 — ITGB3 ・ IL32 — ITGB3 ・ PLA2G2A — ITGB3 ・ SPP1 — ITGB3 ・ TNC — ITGB3 ・ AZGP1 — ITGB3 ・ CCN3 — ITGB3 ・ CD40LG — ITGB3 ・ COL18A1 — ITGB3 ・ COL4A3 — ITGB3 ・ DMP1 — ITGB3 ・ EGFL7 — ITGB3 ・ FCER2 — ITGB3 ・ FGB — ITGB3 ・ FGF1 — ITGB3 ・ FGG — ITGB3 ・ HMGB1 — ITGB3 ・ IBSP — ITGB3 ・ IGF1 — ITGB3 ・ IGF2 — ITGB3 ・ IL1B — ITGB3 ・ L1CAM — ITGB3 ・ LAMA4 — ITGB3 ・ LGALS3 — ITGB3 ・ NRG1 — ITGB3 ・ PECAM1 — ITGB3 ・ PLAUR — ITGB3 ・ POSTN — ITGB3 ・ PTN — ITGB3 ・ RELN — ITGB3 ・ THY1 — ITGB3 ・ VWF — ITGB3