Dataset Information

Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway.

ABSTRACT: Protein tyrosine kinase 7 (PTK7) is a pseudokinase whose precise function in regulating angiogenesis remains unknown. The purpose of this study was to define the mechanisms by which PTK7 promotes vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis in vivo and in vitro. Immunoblotting was used to measure PTK7 expression in several types of vascular endothelial cells. Using both immunoprecipitation and immunoblotting, PTK7 was found to join a receptor complex with Flt-1 (VEGFR1), but not with KDR/Flk-1 (VEGFR2) or with Flt-4 (VEGFR3). By surface plasmon resonance analysis, the interaction between Flt-1 and PTK7 was confirmed and found to be intensified by VEGF-A. Flt-1 phosphorylation and downstream signals of Akt, and focal adhesion kinase (FAK) thus induced were down-regulated by inhibition of PTK7 expression using siRNA. Moreover, PTK7 overexpression in endothelial cells resulted in enhanced angiogenesis in vitro. In contrast, neovascularization induced in vivo by VEGF-A pellets was significantly decreased by injection of siRNA targeting PTK7. These data suggest that PTK7 serves an essential role in Flt-1-mediated angiogenesis.

SUBMITTER: Lee HK

PROVIDER: S-EPMC3110033 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway.

Lee Hyung Keun HK Chauhan Sunil K SK Kay Eunduk E Dana Reza R

Blood 20110401 21

Protein tyrosine kinase 7 (PTK7) is a pseudokinase whose precise function in regulating angiogenesis remains unknown. The purpose of this study was to define the mechanisms by which PTK7 promotes vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis in vivo and in vitro. Immunoblotting was used to measure PTK7 expression in several types of vascular endothelial cells. Using both immunoprecipitation and immunoblotting, PTK7 was found to join a receptor complex with Flt-1 (VEGFR1), bu ...[more]

PMID: 21460247

Similar Datasets

Project description:The collective migration of vascular endothelial cells plays important roles in homeostasis and angiogenesis. Oxygen concentration in vivo, which is lower than in the atmosphere and changes due to diseases, is a key factor affecting the cellular dynamics of vascular endothelial cells. We previously reported that hypoxic conditions promote the internalization of vascular endothelial (VE)-cadherin, a specific cell-cell adhesion molecule, and increase the velocity of the collective migration of vascular endothelial cells. However, the mechanism through which cells regulate collective migration as affected by oxygen tension is not fully understood. Here, we investigated oxygen-dependent collective migration, focusing on intracellular protein p21-activated kinase (PAK) and hypoxia-inducing factor (HIF)-1α. A monolayer of human umbilical vein vascular endothelial cells (HUVECs) was formed in a microfluidic device with controllability of oxygen tension. The HUVECs were then exposed to various oxygen conditions in a range from 0.8% to 21% O2, with or without PAK inhibition or chemical stabilization of HIF-1α. Collective cell migration was measured by particle image velocimetry with time-lapse phase-contrast microscopic images. Localizations of VE-cadherin and HIF-1α were quantified by immunofluorescent staining. The collective migration of HUVECs varied in an oxygen-dependent fashion; the migration speed was increased by hypoxic exposure down to 1% O2, while it decreased under an extremely low oxygen tension of less than 1% O2. PAK inhibition suppressed the hypoxia-induced increase of the migration speed by preventing VE-cadherin internalization into HUVECs. A decrease in the migration speed was also obtained by chemical stabilization of HIF-1α, suggesting that excessive accumulation of HIF-1α diminishes collective cell migration. These results indicate that the oxygen-dependent variation of the migration speed of vascular endothelial cells is mediated by the regulation of VE-cadherin through the PAK pathway, as well as other mechanisms via HIF-1α, especially under extreme hypoxic conditions.

Dataset Information

Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway.

Publications

Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets