Vascular endothelial growth factor receptor-2: Structure, function, intracellular signalling and therapeutic inhibition

Tumor Angiogenesis: Therapeutic Implications

1971 • 9,898 citations

Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor

1999 • 6,443 citations

The Phosphoinositide 3-Kinase Pathway

2002 • 5,427 citations

Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy

2005 • 5,086 citations

Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis

1992 • 4,631 citations

Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele

1996 • 4,143 citations

Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice

1995 • 3,977 citations

Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid

1983 • 3,942 citations

BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis

2004 • 3,873 citations

Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene

1996 • 3,664 citations

The small GTP-binding protein rac regulates growth factor-induced membrane ruffling

1992 • 3,628 citations

Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation

1999 • 3,529 citations

Regulation of Cell Death Protease Caspase-9 by Phosphorylation

1998 • 3,129 citations

VEGF receptor signalling ? in control of vascular function

2006 • 2,930 citations

Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis

2000 • 2,700 citations

SH2 domains recognize specific phosphopeptide sequences

1993 • 2,685 citations

Regulation of endothelium-derived nitric oxide production by the protein kinase Akt

1999 • 2,577 citations

Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels

1994 • 2,293 citations

Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells

1989 • 2,267 citations

Vascular Endothelial Growth Factor Regulates Endothelial Cell Survival through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction Pathway

1998 • 1,963 citations

High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis

1993 • 1,961 citations

In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship.

2003 • 1,939 citations

Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.

1997 • 1,590 citations

Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy

2002 • 1,549 citations

Focal adhesion kinase: the first ten years

2003 • 1,360 citations

The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.

1993 • 1,114 citations

Lessons from phase III clinical trials on anti-VEGF therapy for cancer

2006 • 1,044 citations

Hypoxia Regulates Vascular Endothelial Growth Factor Gene Expression in Endothelial Cells

1995 • 1,001 citations

Vascular Endothelial Growth Factor Induces Expression of the Antiapoptotic Proteins Bcl-2 and A1 in Vascular Endothelial Cells

1998 • 996 citations

Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability

2001 • 960 citations

The splice variants of vascular endothelial growth factor (VEGF) and their receptors

2001 • 943 citations

Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy

2005 • 930 citations

Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.

1992 • 900 citations

Selective Requirement for Src Kinases during VEGF-Induced Angiogenesis and Vascular Permeability

1999 • 802 citations

ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration.

2002 • 784 citations

A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells

2001 • 729 citations

flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors

1993 • 707 citations

AZD2171: A Highly Potent, Orally Bioavailable, Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer

2005 • 704 citations

Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors

2005 • 687 citations

Bevacizumab in Combination With Fluorouracil and Leucovorin: An Active Regimen for First-Line Metastatic Colorectal Cancer

2005 • 673 citations

Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family

2001 • 662 citations

Role of αvβ3 integrin in the activation of vascular endothelial growth factor receptor-2

1999 • 597 citations

Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth.

1996 • 567 citations

VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells

1999 • 563 citations

VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma.

2002 • 547 citations

Identification of a new endothelial cell growth factor receptor tyrosine kinase

1991 • 529 citations

Angiogenesis promoted by vascular endothelial growth factor: Regulation through α₁β₁and α₂β₁ integrins

1997 • 516 citations

A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit.

1991 • 516 citations

Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis.

1993 • 502 citations

Assignment of the Vascular Endothelial Growth Factor Gene to Human Chromosome 6p21.3

1996 • 473 citations

Vascular Endothelial Growth Factors

2007 • 464 citations

VEGF₁₆₅ mediates formation of complexes containing VEGFR‐2 and neuropilin‐1 that enhance VEGF₁₆₅‐receptor binding

2002 • 456 citations

Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site

1997 • 443 citations

Marked Induction of the IAP Family Antiapoptotic Proteins Survivin and XIAP by VEGF in Vascular Endothelial Cells

1999 • 342 citations

Safety and Pharmacokinetics of the Dual Action Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor, BAY 43-9006, in Patients with Advanced, Refractory Solid Tumors

2005 • 335 citations

Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice

2005 • 318 citations

Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation.

1995 • 311 citations

Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus

1994 • 310 citations

The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-γ pathway and partially induces mitotic signals in NIH3T3 fibroblasts

1997 • 305 citations

Vascular Endothelial Growth Factor Receptor-2 and Neuropilin-1 Form a Receptor Complex That Is Responsible for the Differential Signaling Potency of VEGF165 and VEGF121

2001 • 298 citations

VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis

2005 • 281 citations

Sphingosine Kinase Mediates Vascular Endothelial Growth Factor-Induced Activation of Ras and Mitogen-Activated Protein Kinases

2002 • 275 citations

Vascular Endothelial Growth Factor Induction of the Angiogenic Phenotype Requires Ras Activation

2001 • 261 citations

Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A₂ in endothelial cells via p42/p44 mitogen‐activated protein kinase

1997 • 258 citations

Requirements for Binding and Signaling of the Kinase Domain Receptor for Vascular Endothelial Growth Factor

1998 • 256 citations

The Adaptor Protein Shb Binds to Tyrosine 1175 in Vascular Endothelial Growth Factor (VEGF) Receptor-2 and Regulates VEGF-dependent Cellular Migration

2004 • 255 citations

Essential role of the tyrosine kinase substrate phospholipase C-γ1 in mammalian growth and development

1997 • 251 citations

Regulation of microvascular permeability by vascular endothelial growth factors*

2002 • 250 citations

Molecular and functional diversity of vascular endothelial growth factors

2006 • 248 citations

phospholipase C gamma-1is required downstream ofvascular endothelial growth factorduring arterial development

2003 • 234 citations

Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38

2004 • 214 citations

Intrinsic Tyrosine Kinase Activity is Required for Vascular Endothelial Growth Factor Receptor 2 Ubiquitination, Sorting and Degradation in Endothelial Cells

2006 • 177 citations

Phosphorylation of Tyr1214 within VEGFR-2 Triggers the Recruitment of Nck and Activation of Fyn Leading to SAPK2/p38 Activation and Endothelial Cell Migration in Response to VEGF

2006 • 170 citations

Vascular Endothelial Growth Factor–Regulated Gene Expression in Endothelial Cells

2003 • 167 citations

Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells

2003 • 160 citations

Structure of a VEGF–VEGF receptor complex determined by electron microscopy

2007 • 150 citations

Mapping of the Sites Involved in Ligand Association and Dissociation at the Extracellular Domain of the Kinase Insert Domain-containing Receptor for Vascular Endothelial Growth Factor

1998 • 145 citations

Antivascular Endothelial Growth Factor Agents and Their Development: Therapeutic Implications in Ocular Diseases

2006 • 140 citations

Neuropilin-1 Regulates Vascular Endothelial Growth Factor–Mediated Endothelial Permeability

2005 • 137 citations

Absence of Erythrogenesis and Vasculogenesis in Plcg1-deficient Mice

2002 • 137 citations

Snake Venom Vascular Endothelial Growth Factors (VEGFs) Exhibit Potent Activity through Their Specific Recognition of KDR (VEGF Receptor 2)

2003 • 133 citations

Vascular Endothelial Growth Factor Receptor KDR Tyrosine Kinase Activity Is Increased by Autophosphorylation of Two Activation Loop Tyrosine Residues

1999 • 128 citations

Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer

2007 • 126 citations

cDNA microarray analysis of the gene expression profile of VEGF-activated human umbilical vein endothelial cells.

2001 • 124 citations

Properties of Two VEGF Receptors, Flt‐1 and KDR, in Signal Transduction^a

2000 • 123 citations

VRAP Is an Adaptor Protein That Binds KDR, a Receptor for Vascular Endothelial Cell Growth Factor

2000 • 120 citations

KDR (VEGF Receptor 2) Is the Major Mediator for the Hypotensive Effect of VEGF

2002 • 119 citations

Is angiogenesis an organizing principle in biology and medicine?

2007 • 118 citations

Biological Activity and Phosphorylation Sites of the Bacterially Expressed Cytosolic Domain of the KDR VEGF-Receptor

1994 • 112 citations

Angiogenesis: a curse or cure?

2005 • 109 citations

Covalent dimerization of vascular permeability factor/vascular endothelial growth factor is essential for its biological activity. Evidence from Cys to Ser mutations

1994 • 103 citations

The Scaffolding Adapter Gab1 Mediates Vascular Endothelial Growth Factor Signaling and Is Required for Endothelial Cell Migration and Capillary Formation

2006 • 101 citations

Vascular endothelial growth factor-induced prostacyclin production is mediated by a protein kinase C (PKC)-dependent activation of extracellular signal-regulated protein kinases 1 and 2 involving PKC-δ and by mobilization of intracellular Ca2+

2001 • 98 citations

Analysis of VEGF-responsive genes involved in the activation of endothelial cells.

2003 • 91 citations

Interactions of FLT-1 and KDR with Phospholipase C γ: Identification of the Phosphotyrosine Binding Sites

1997 • 88 citations

A review of the latest clinical compounds to inhibit VEGF in pathological angiogenesis

2006 • 86 citations

Down Syndrome Candidate Region 1,a Downstream Target of VEGF, Participa tes in Endothelial Cell Migration and Angiogenesis

2004 • 84 citations

The Carboxyl Terminus of VEGFR-2 Is Required for PKC-mediated Down-Regulation

2005 • 81 citations

The Proliferative Effect of Vascular Endothelial Growth Factor Requires Protein Kinase C-α and Protein Kinase C-ζ

1999 • 78 citations

The Shc-related adaptor protein, Sck, forms a complex with the vascular-endothelial-growth-factor receptor KDR in transfected cells

2000 • 75 citations

The Adaptor Protein Gab1 Couples the Stimulation of Vascular Endothelial Growth Factor Receptor-2 to the Activation of Phosphoinositide 3-Kinase

2006 • 63 citations

VEGF, flt-1, and KDR/flk-1 as Prognostic Indicators in Endometrial Carcinoma

2000 • 62 citations

PTK 787/ZK 222584, a Tyrosine Kinase Inhibitor of all Known VEGF Receptors, Represses Tumor Growth with High Efficacy

2005 • 62 citations

Microarray analysis of VEGF-responsive genes in myometrial endothelial cells

2002 • 58 citations

Induction of endothelial cell decay-accelerating factor by vascular endothelial growth factor: A mechanism for cytoprotection against complement-mediated injury during inflammatory angiogenesis

2001 • 55 citations

The Presence of a Single Tyrosine Residue at the Carboxyl Domain of Vascular Endothelial Growth Factor Receptor-2/FLK-1 Regulates Its Autophosphorylation and Activation of Signaling Molecules

2002 • 46 citations

Vascular endothelial growth factor in amyotrophic lateral sclerosis and other neurodegenerative diseases

2006 • 44 citations

The Shb adaptor protein causes Src-dependent cell spreading and activation of focal adhesion kinase in murine brain endothelial cells

2002 • 42 citations

Vascular Endothelial Growth Factor Receptor Family Genes: When Did the Three Genes Phylogenetically Segregate?

2002 • 39 citations

[Receptors for factors of the VEGF (Vascular Endothelial Growth Family)].

1997 • 21 citations

The kinase insert domain receptor gene (KDR) has been relocated to chromosome 4q11→q12

1995 • 19 citations