The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells.

Puri, Mira C.; Rossant, Janet; Alitalo, Kari; Bernstein, Alan; Partanen, Juha

doi:10.1002/j.1460-2075.1995.tb00276.x

Cited by 462 publications

(299 citation statements)

References 25 publications

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“…On average, 6 to 8 fields were taken from each section. Results were expressed as mean number of vWF-positive vessels per mm 2 .…”

Section: The Matrigel Plug Assay To Assess In Vivo Angiogenesismentioning

confidence: 99%

“…1 Tie2 signaling has been shown to be required for later stages of embryonic blood vessel development, [2][3][4] including vascular remodeling, vessel integrity, and maturation. 1,5 In vitro experiments have shown that Ang1 induces endothelial cell (EC) sprouting in vitro, 6,7 and stimulates EC migration 8 and the formation and stabilization of capillary-like networks in culture systems.…”

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confidence: 99%

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Angiogenic Actions of Angiopoietin-1 Require Endothelium-Derived Nitric Oxide

Babaei

Teichert-Kuliszewska

Zhang

et al. 2003

The American Journal of Pathology

166

140

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Angiopoietin1 (Ang1) is a novel angiogenic factor with important actions on endothelial cell (EC) differentiation and vascular maturation. Ang1 has been shown to prevent EC apoptosis through activation of PI3-kinase/ Akt, a pathway that is also known to activate endothelium nitric oxide synthase (eNOS). Therefore, we hypothesized that the angiogenic effects of Ang1 would also be dependent on the PI3-kinase/Akt pathway, possibly mediated by increased eNOS activity and NO release. Treatment of human umbilical vein endothelial cells with recombinant Ang1* (300 ng/ml) for 15 minutes resulted in PI3-kinase-dependent Akt phosphorylation, comparable to that observed with vascular endothelial growth factor (VEGF) (50 ng/ml), and increased NO production in a PI3-kinase/Akt-dependent manner. Capillary-like tube formation induced by Ang1* in fibrin matrix at 24 hours (differentiation index, DI: 13.74 ؎ 0.76 versus control 1.71 ؎ 0.31) was abolished in the presence of the selective PI3-kinase inhibitor, LY294002 (50 mol/L) (DI: 0.31 ؎ 0.31, P < 0.01) or the NOS inhibitor, L-NAME (3 mmol/L) (DI: 4.10 ؎ 0.59, P < 0.01). In subcutaneous Matrigel implants in vivo, addition of recombinant Ang1* or wild-type Ang1 from conditioned media of COS-1 cells transfected with a pFLAG Ang1 expression vector, induced significant neovascularization to a degree similar to VEGF. Finally, angiogenesis in vivo in response to both Ang1 and VEGF was significantly reduced in eNOS-deficient compared with wild-type mice. In summary, our results demonstrate for the first time that endothelialderived NO is required for Ang1-induced angiogenesis, and that the PI3-kinase signaling mediates the activation of eNOS and NO release in response to

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“…On average, 6 to 8 fields were taken from each section. Results were expressed as mean number of vWF-positive vessels per mm 2 .…”

Section: The Matrigel Plug Assay To Assess In Vivo Angiogenesismentioning

confidence: 99%

mentioning

confidence: 99%

Angiogenic Actions of Angiopoietin-1 Require Endothelium-Derived Nitric Oxide

Babaei

Teichert-Kuliszewska

Zhang

et al. 2003

The American Journal of Pathology

166

140

View full text Add to dashboard Cite

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“…Targeted null mutations in all of these receptors result in embryonic lethality (Shalaby et al, 1995;Fong et al, 1995;Dumont et al, in prep. ;Dumont et al, 1994;Sato et al, 1995;Puri et al, 1995), and the lethal phenotype is distinct for each receptor. These results suggest that the signaling pathways that are mediated by these receptors play unique roles in development.…”

Section: Introductionmentioning

confidence: 99%

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R

1998

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Tek/Tie2 is an endothelial cell-speci®c receptor tyrosine kinase that has been shown to play a role in vascular development of the mouse. Targeted mutagenesis of both Tek and its agonistic ligand, Angiopoietin-1, result in embryonic lethality, demonstrating that the signal transduction pathway(s) mediated by this receptor are crucial for normal embryonic development. In an attempt to identify downstream signaling partners of the Tek receptor, we have used the yeast two-hybrid system to identify phosphotyrosine-dependent interactions. Using this approach, we have identi®ed a novel docking molecule called Dok-R, which has sequence and structural homology to p62 dok and IRS-3. Mapping of the phosphotyrosine-interaction domain within Dok-R shows that Dok-R interacts with Tek through a PTB domain. Dok-R is coexpressed with Tek in a number of endothelial cell lines. We show that coexpression of Dok-R with activated Tek results in tyrosine phosphorylation of Dok-R and that rasGAP and Nck coimmunoprecipitate with phosphorylated Dok-R. Furthermore, Dok-R is constitutively bound to Crk presumably through the proline rich tail of Dok-R. The cloning of Dok-R represents the ®rst downstream substrate of the activated Tek receptor, and suggests that Tek can signal through a multitude of pathways.

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“…Tie-1 and tie-2 deficient mice die at later times than VEGF receptor null mice, exhibiting phenotypical alterations consistent with a role in vascular remodeling. 21,23,24 Ang-1 and Ang-2 are secreted glycoproteins that share ϳ60% amino acid identity and bind with similar affinity to tie-2. Although Ang-1 induces autophosphorylation of tie-2, Ang-2 is a naturally occurring antagonist that blocks Ang-1-induced tie-2 autophosphorylation.…”

mentioning

confidence: 99%