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PMID:16403913

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Citation

Huang, Y, Shi, H, Zhou, H, Song, X, Yuan, S and Luo, Y (2006) The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood 107:3564-71

Abstract

Nucleolin, originally described as a nuclear protein, was recently found to be expressed on the surface of endothelial cells during angiogenic. However, the functions of cell-surface nucleolin in angiogenic remain mysterious. Here we report that upon endothelial cells adhering to extracellular matrix components, vascular endothelial growth factor (VEGF) mobilizes nucleolin from nucleus to cell surface. Functional blockage or down-regulation of the expression of cell-surface nucleolin in endothelial cells significantly inhibits the migration of endothelial cells and prevents capillary-tubule formation. Moreover, nonmuscle myosin heavy chain 9 (MyH9), an actin-based motor protein, is identified as a nucleolin-binding protein. Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin. Knocking down endogenous MyH9, specifically inhibiting myosin activity, or overexpressing functional deficient MyH9 disrupts the organization of cell-surface nucleolin and inhibits its angiogenic function. These studies indicate that VEGF, extracellular matrix, and intracellular motor protein MyH9 are all essential for the novel function of nucleolin in angiogenic.

Links

PubMed Online version:10.1182/blood-2005-07-2961

Keywords

Active Transport, Cell Nucleus; Cells, Cultured; Extracellular Matrix/metabolism; Humans; Molecular Motor Proteins/antagonists & inhibitors; Molecular Motor Proteins/genetics; Molecular Motor Proteins/physiology; Myosin Heavy Chains/antagonists & inhibitors; Myosin Heavy Chains/genetics; Myosin Heavy Chains/physiology; Neovascularization, Physiologic; Phosphoproteins/antagonists & inhibitors; Phosphoproteins/genetics; Phosphoproteins/physiology; RNA Interference; RNA-Binding Proteins/antagonists & inhibitors; RNA-Binding Proteins/genetics; RNA-Binding Proteins/physiology; Vascular Endothelial Growth Factor A/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NUCL

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35579

F

Seeded From UniProt

complete

HUMAN:NUCL

located_in

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYH9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19338

F

Seeded From UniProt

complete

HUMAN:MYH9

involved_in

GO:0001525: angiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYH9

located_in

GO:0001726: ruffle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYH9

located_in

GO:0001725: stress fiber

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYH9

involved_in

GO:0015031: protein transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYH9

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYH9

involved_in

GO:0043534: blood vessel endothelial cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYH9

enables

GO:0043495: protein-membrane adaptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MYH9

enables

GO:0051015: actin filament binding

ECO:0000303: author statement without traceable support used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NUCL

enables

GO:0008022: protein C-terminus binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35579

F

Seeded From UniProt

complete

HUMAN:NUCL

part_of

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NUCL

involved_in

GO:0001525: angiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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