| Structural highlights
Function
VGFR2_MOUSE Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as a negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and by preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.[1] [2] [3] [4] [5] [6] [7] [8]
References
- ↑ Meyer RD, Dayanir V, Majnoun F, Rahimi N. The presence of a single tyrosine residue at the carboxyl domain of vascular endothelial growth factor receptor-2/FLK-1 regulates its autophosphorylation and activation of signaling molecules. J Biol Chem. 2002 Jul 26;277(30):27081-7. doi: 10.1074/jbc.M110544200. Epub 2002 , May 22. PMID:12023952 doi:https://dx.doi.org/10.1074/jbc.M110544200
- ↑ Singh AJ, Meyer RD, Band H, Rahimi N. The carboxyl terminus of VEGFR-2 is required for PKC-mediated down-regulation. Mol Biol Cell. 2005 Apr;16(4):2106-18. doi: 10.1091/mbc.e04-08-0749. Epub 2005 , Jan 26. PMID:15673613 doi:https://dx.doi.org/10.1091/mbc.e04-08-0749
- ↑ Kanemura H, Satoh T, Bilasy SE, Ueda S, Hirashima M, Kataoka T. Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1. Biochem Biophys Res Commun. 2009 Oct 2;387(4):754-9. PMID:19635461 doi:10.1016/j.bbrc.2009.07.108
- ↑ Facemire CS, Nixon AB, Griffiths R, Hurwitz H, Coffman TM. Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide synthase expression. Hypertension. 2009 Sep;54(3):652-8. PMID:19652084 doi:10.1161/HYPERTENSIONAHA.109.129973
- ↑ Albuquerque RJ, Hayashi T, Cho WG, Kleinman ME, Dridi S, Takeda A, Baffi JZ, Yamada K, Kaneko H, Green MG, Chappell J, Wilting J, Weich HA, Yamagami S, Amano S, Mizuki N, Alexander JS, Peterson ML, Brekken RA, Hirashima M, Capoor S, Usui T, Ambati BK, Ambati J. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med. 2009 Sep;15(9):1023-30. doi: 10.1038/nm.2018. Epub 2009 Aug 9. PMID:19668192 doi:10.1038/nm.2018
- ↑ Nakao S, Zandi S, Hata Y, Kawahara S, Arita R, Schering A, Sun D, Melhorn MI, Ito Y, Lara-Castillo N, Ishibashi T, Hafezi-Moghadam A. Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph- and angiogenesis. Blood. 2011 Jan 20;117(3):1081-90. doi: 10.1182/blood-2010-02-267427. Epub 2010, Aug 12. PMID:20705758 doi:10.1182/blood-2010-02-267427
- ↑ Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995 Jul 6;376(6535):62-6. PMID:7596435 doi:10.1038/376062a0
- ↑ Quinn TP, Peters KG, De Vries C, Ferrara N, Williams LT. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7533-7. PMID:8356051 doi:10.1073/pnas.90.16.7533
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