The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function.

Vascular endothelial growth factor receptor 2 (VEGFR2, encoded by KDR) regulates endothelial function and angiogenesis. VEGFR2 undergoes ubiquitination that programs this receptor for trafficking and proteolysis, but the ubiquitin-modifying enzymes involved are ill-defined. Herein, we used a reverse genetics screen for the human E2 family of ubiquitin-conjugating enzymes to identify gene products that regulate VEGFR2 ubiquitination and proteolysis.

Mechanisms of whole smoke conditioned media induced cytotoxicity to human aortic endothelial cells.

Chronic exposure to cigarette smoke can lead to endothelial dysfunction and potentially endothelial cell death. Here, we exposed Human Aortic Endothelial Cells (HAECs) to whole smoke conditioned media (WSCM) over a range of nicotine equivalence (n.e.

Human aortic endothelial cells respond to shear flow in well-plate microfluidic devices.

Although chronic progressive cardiovascular diseases such as atherosclerosis are often challenging to fully model in vitro, it has been shown that certain in vitro methods can effectively evaluate some aspects of disease progression. This has been demonstrated in in vitro and in vivo studies of endothelial cells that have illustrated the effects of nitric oxide (NO) production, filamentous actin (F-actin) formation, and cell and actin angle alignment on vascular function and homeostasis. Systems utilising shear flow have been established, in order to create a physiologically relevant environment for cells that require shear flow for homeostasis.

Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function.

Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response.

VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes.

Extracellular and Luminal pH Regulation by Vacuolar H+-ATPase Isoform Expression and Targeting to the Plasma Membrane and Endosomes.

Plasma membrane vacuolar H(+)-ATPase (V-ATPase) activity of tumor cells is a major factor in control of cytoplasmic and extracellular pH and metastatic potential, but the isoforms involved and the factors governing plasma membrane recruitment remain uncertain. Here, we examined expression, distribution, and activity of V-ATPase isoforms in invasive prostate adenocarcinoma (PC-3) cells. Isoforms 1 and 3 were the most highly expressed forms of membrane subunit a, with a1 and a3 the dominant plasma membrane isoforms.

VEGFR2 Trafficking, Signaling and Proteolysis is Regulated by the Ubiquitin Isopeptidase USP8.

Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular function. VEGF-A binding to vascular endothelial growth factor receptor 2 (VEGFR2) stimulates endothelial signal transduction and regulates multiple cellular responses. Activated VEGFR2 undergoes ubiquitination but the enzymes that regulate this post-translational modification are unclear.

The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors.

Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival.

Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells.

The vascular endothelial growth factor A (VEGF-A) is a multifunctional cytokine that stimulates blood vessel sprouting, vascular repair, and regeneration. VEGF-A binds to VEGF receptor tyrosine kinases (VEGFRs) and stimulates intracellular signaling leading to changes in vascular physiology. An important aspect of this phenomenon is the spatiotemporal coordination of VEGFR trafficking and intracellular signaling to ensure that VEGFR residence in different organelles is linked to downstream cellular outputs.