RGD Reference Report - TAK1 kinase signaling regulates embryonic angiogenesis by modulating endothelial cell survival and migration. - Rat Genome Database

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TAK1 kinase signaling regulates embryonic angiogenesis by modulating endothelial cell survival and migration.

Authors: Morioka, Sho  Inagaki, Maiko  Komatsu, Yoshihiro  Mishina, Yuji  Matsumoto, Kunihiro  Ninomiya-Tsuji, Jun 
Citation: Morioka S, etal., Blood. 2012 Nov 1;120(18):3846-57. doi: 10.1182/blood-2012-03-416198. Epub 2012 Sep 12.
RGD ID: 155663421
Pubmed: PMID:22972987   (View Abstract at PubMed)
PMCID: PMC3488895   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2012-03-416198   (Journal Full-text)

TGF-β activated kinase 1 (TAK1) is a mediator of various cytokine signaling pathways. Germline deficiency of Tak1 causes multiple abnormalities, including dilated blood vessels at midgestation. However, the mechanisms by which TAK1 regulates vessel formation have not been elucidated. TAK1 binding proteins 1 and 2 (TAB1 and TAB2) are activators of TAK1, but their roles in embryonic TAK1 signaling have not been determined. In the present study, we characterized mouse embryos harboring endothelial-specific deletions of Tak1, Tab1, or Tab2 and found that endothelial TAK1 and TAB2, but not TAB1, were critically involved in vascular formation. TAK1 deficiency in endothelial cells caused increased cell death and vessel regression at embryonic day 10.5 (E10.5). Deletion of TNF signaling largely rescued endothelial cell death in TAK1-deficient embryos at E10.5. However, embryos deficient in both TAK1 and TNF signaling still exhibited dilated capillary networks at E12.5. TAB2 deficiency caused reduced TAK1 activity, resulting in abnormal capillary blood vessels, similar to the compound deficiency of TAK1 and TNF signaling. Ablation of either TAK1 or TAB2 impaired cell migration and tube formation. Our results show that endothelial TAK1 signaling is important for 2 biologic processes in angiogenesis: inhibiting TNF-dependent endothelial cell death and promoting TNF-independent angiogenic cell migration.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Map3k7  (mitogen activated protein kinase kinase kinase 7)
Tab2  (TGF-beta activated kinase 1/MAP3K7 binding protein 2)
Tnfrsf1a  (TNF receptor superfamily member 1A)

Genes (Mus musculus)
Map3k7  (mitogen-activated protein kinase kinase kinase 7)
Tab2  (TGF-beta activated kinase 1/MAP3K7 binding protein 2)
Tnfrsf1a  (tumor necrosis factor receptor superfamily, member 1a)

Genes (Homo sapiens)
MAP3K7  (mitogen-activated protein kinase kinase kinase 7)
TAB2  (TGF-beta activated kinase 1 (MAP3K7) binding protein 2)
TNFRSF1A  (TNF receptor superfamily member 1A)


Additional Information