8.A.245.  The Vascular Endothelial Growth Factor (VEGF) Family 

Members participate in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A (Katsman et al. 2022).  It is also involved in protecting cells from hypoxia-mediated cell death.  It is active in angiogenesis, vasculogenesis and endothelial cell growth (Lee et al. 2021), and induces permeabilization of blood vessels, while preventing the downregulation of KCC2 induced by axotomy in extraocular motoneurons (Capilla-López et al. 2024).  The potassium-chloride cotransporter KCC2 is the main extruder of Cl- in neurons. It plays a fundamental role in the activity of the inhibitory neurotransmitters (GABA and glycine) since low levels of KCC2 promote intracellular Cl- accumulation, leading to the depolarizing activity of GABA and glycine. (See 2.A.30.1.14 and 18 for KCC2 descriptions.)


 

References:

Capilla-López, J., R.G. Hernández, G. Carrero-Rojas, P.M. Calvo, F.J. Alvarez, R.R. de la Cruz, and A.M. Pastor. (2024). VEGF, but Not BDNF, Prevents the Downregulation of KCC2 Induced by Axotomy in Extraocular Motoneurons. Int J Mol Sci 25:.
Katsman, M., A. Azriel, G. Horev, Y. Reizel, and B.Z. Levi. (2022). N-VEGF, the Autoregulatory Arm of VEGF-A. Cells 11:.
Lee, J.W., J. Hur, Y.W. Kwon, C.W. Chae, J.I. Choi, I. Hwang, J.Y. Yun, J.A. Kang, Y.E. Choi, Y.H. Kim, S.E. Lee, C. Lee, D.H. Jo, H. Seok, B.S. Cho, S.H. Baek, and H.S. Kim. (2021). KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state. J Hematol Oncol 14: 148.
Leppänen, V.M., M. Jeltsch, A. Anisimov, D. Tvorogov, K. Aho, N. Kalkkinen, P. Toivanen, S. Ylä-Herttuala, K. Ballmer-Hofer, and K. Alitalo. (2011). Structural determinants of vascular endothelial growth factor-D receptor binding and specificity. Blood 117: 1507-1515.
Examples:

TC#NameOrganismal TypeExample
8.A.245.1.1

VEGFA of 395 aas with two possible TMSs at residies 50 and 190.  It induces permeabilization of blood vessels while preventing the downregulation of KCC2 induced by axotomy in extraocular motoneurons (Capilla-López et al. 2024).

VEGFA of Homo sapiens

 
8.A.245.1.2

Vascular endothelial growth factor B, VEGFB, of 207 aas with 1 N-terminal TMS, and possibly one at residue 60. It is a growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis.

VEGFB of Homo sapiens

 
8.A.245.1.3

Vascular endothelial growth factor C (4), VEGF4, of 419aas and 1 N-terminal TMS. It is a growth factor active in angiogenesis as well as endothelial cell growth, stimulating their proliferation and migration. It also has effects on the permeability of blood vessels, and may function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis. It also plays a role in the maintenance of differentiated lymphatic endothelium in adults, and binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors.

Animals

VEGFC of Homo sapiens (P49767)

 
8.A.245.1.4

VEGFD of 354 aas and 1 N-terminal TMS.  It binds and activates VEGFR-2 (KDR/FLK1) and VEGFR-3 (FLT4) receptors (Leppänen et al. 2011).

VEGFD of Homo sapiens