ArticleProceedings of the National Academy of Sciences of the United States of America2011
Grb-2-associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A-endothelial NOS pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- Epithelial Gab1 Restricts Sepsis-Induced Intestinal Injury by Orchestrating TNF/NF-κB Axis.Mediators of inflammation · 2026Article
- VEGF-B-mediated myofiber types involved in high-fat diet-induced hyperglycemia through PKA-NFATs signaling pathway.Stem cell research & therapy · 2025Article
- The Role of GAB1 in Cancer.Cancers · 2023Review
- Antipsychotics impair regulation of glucose metabolism by central glucose.Molecular psychiatry · 2022Article
- Vascular and Liver Homeostasis in Juvenile Mice Require Endothelial Cyclic AMP-Dependent Protein Kinase A.International journal of molecular sciences · 2022Article
- Nephronectin promotes cardiac repair post myocardial infarction via activating EGFR/JAK2/STAT3 pathway.International journal of medical sciences · 2022Article
- Endothelial deletion of SHP2 suppresses tumor angiogenesis and promotes vascular normalization.Nature communications · 2021Article
- Therapeutic Effects and Associated Mechanisms by which "Fuyang Jiedu Huayu" Granules Treat Chronic Liver Failure in the Rat.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Extracellular adenosine enhances pulmonary artery vasa vasorum endothelial cell barrier function via Gi/ELMO1/Rac1/PKA-dependent signaling mechanisms.American journal of physiology. Cell physiology · 2020Article
- Regeneration Enhances Metastasis: A Novel Role for Neurovascular Signaling in Promoting Melanoma Brain Metastasis.Frontiers in neuroscience · 2019Article
- Cholinergic Grb2-Associated-Binding Protein 1 Regulates Cognitive Function.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Gαi1 and Gαi3mediate VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.Theranostics · 2018Article
- Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma.Cell research · 2016Article
- cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner.Development (Cambridge, England) · 2016Article
- CdGAP/ARHGAP31, a Cdc42/Rac1 GTPase regulator, is critical for vascular development and VEGF-mediated angiogenesis.Scientific reports · 2016Article
- Minicircle DNA-mediated endothelial nitric oxide synthase gene transfer enhances angiogenic responses of bone marrow-derived mesenchymal stem cells.Stem cell research & therapy · 2016Article
- Cardiac Gab1 deletion leads to dilated cardiomyopathy associated with mitochondrial damage and cardiomyocyte apoptosis.Cell death and differentiation · 2016Article
- Article
- PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling.Cellular signalling · 2016Article
- Deficient angiogenesis in redox-dead Cys17Ser PKARIα knock-in mice.Nature communications · 2015Article
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Authors and funding
17 authors at 7 institutions in 5 countries.
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Abstract
The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood. Herein we show that Grb-2-associated binder 1 (Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis. Endothelium-specific Gab1 KO (EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression. Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice. The vessels and endothelial cells (ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF. Biochemical analyses revealed a substantial reduction of endothelial NOS (eNOS) activation in Gab1-deficient vessels and ECs following VEGF stimulation. Interestingly, the phosphorylation of Akt, an enzyme known to promote VEGF-induced eNOS activation, was increased in Gab1-deficient vessels and ECs whereas protein kinase A (PKA) activity was significantly decreased. Introduction of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ECs. Reexpression of WT or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and eNOS. Taken together, these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation, which is dependent on PKA. Of note, this pathway is conserved in primary human ECs for VEGF-induced eNOS activation and tube formation, suggesting considerable potential in treatment of human ischemic diseases.
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