CDB25:0004449 VWF — 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

Selective inactivation of the Arg-Gly-Asp-Ser (RGDS) binding site in von Willebrand factor by site-directed mutagenesis.

The Journal of biological chemistry, 1992; PubMed, Homo sapiens VWF — Homo sapiens ITGB3

ABSTRACT: In order to assess the requirement for the Arg-Gly-Asp-Ser (RGDS) consensus adhesion sequence in von Willebrand factor (vWF) for vWF binding to platelets and endothelial cells, point mutations were introduced into this sequence by site-directed mutagenesis. A glycine to alanine substitution yielded RADS-vWF, while an aspartate to glutamate substitution resulted in RGES-vWF. Recombinant RADS-vWF and RGES-vWF, purified from transformed Chinese hamster ovary cells, were compared with recombinant wild type vWF (WT-vWF) in functional assays with platelets and human umbilical vein endothelial cells (HU-VECs). High molecular weight RADS-vWF and RGES-vWF multimers inhibited binding of 125I-vWF to a mixture of insolubilized native type I and III collagen and competed effectively with 125I-vWF for binding to formalin-fixed platelets in the presence of ristocetin, indicating functional collagen and platelet glycoprotein Ib binding. However, RADS-vWF and RGES-vWF were unable to displace the binding of 125I-vWF to thrombin or ADP-activated platelets. The attachment of HUVECs to either RADS-vWF or RGES-vWF coated surfaces was reduced and spreading was almost completely inhibited, compared with WT-vWF. We conclude that point mutations of the RGDS sequence in vWF selectively impair binding to platelet glycoprotein IIb/IIIa and the HUVEC vitronectin receptor.

Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress.

Blood, 2009; PubMed, Homo sapiens VWF — Homo sapiens ITGB3

ABSTRACT: Acutely secreted von Willebrand factor (VWF) multimers adhere to endothelial cells, support platelet adhesion, and may induce microvascular thrombosis. Immunofluorescence microscopy of live human umbilical vein endothelial cells showed that VWF multimers rapidly formed strings several hundred micrometers long on the cell surface after stimulation with histamine. Unexpectedly, only a subset of VWF strings supported platelet binding, which depended on platelet glycoprotein Ib. Electron microscopy showed that VWF strings often consisted of bundles and networks of VWF multimers, and each string was tethered to the cell surface by a limited number of sites. Several approaches implicated P-selectin and integrin alpha(v)beta(3) in anchoring VWF strings. An RGDS peptide or a function-blocking antibody to integrin alpha(v)beta(3) reduced the number of VWF strings formed. In addition, integrin alpha(v) decorated the VWF strings by immunofluorescence microscopy. Furthermore, lentiviral transduction of shRNA against the alpha(v) subunit reduced the expression of cell-surface integrin alpha(v)beta(3) and impaired the ability of endothelial cells to retain VWF strings. Soluble P-selectin reduced the number of platelet-decorated VWF strings in the absence of Ca(2+) and Mg(2+) but had no effect in the presence of these cations. These results indicate that VWF strings bind specifically to integrin alpha(v)beta(3) on human endothelial cells.

Basic Information on VWF

Ligand Name: von Willebrand factor

Other Symbols: F8VWF

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: VWF

GeneCards: VWF

HGNC Gene Group: Receptor ligands

Functional Annotations for VWF

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 VWF

VWF — GP1BA ・ VWF — ITGA2B ・ VWF — SELP ・ VWF — CLEC4M ・ VWF — GP9 ・ VWF — ITGA4 ・ VWF — ITGA9 ・ VWF — ITGAV ・ VWF — ITGB1 ・ VWF — LRP1 ・ VWF — SCARA5 ・ VWF — STAB2

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 ・ FGF2 — 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