Vascular endothelial growth factor C

Rendering based on PDB 2X1W.

Available structures
PDB	2X1W, 2X1X

Identifiers

Symbols

VEGFC; Flt4-L; VRP

External IDs

OMIM: 601528 MGI: 109124 HomoloGene: 3962 GeneCards: VEGFC Gene

Gene Ontology
Molecular function	• protein binding • growth factor activity • chemoattractant activity • vascular endothelial growth factor receptor 3 binding
Cellular component	• extracellular region • extracellular space • membrane • platelet alpha granule lumen
Biological process	• angiogenesis • positive regulation of neuroblast proliferation • platelet degranulation • substrate-dependent cell migration • signal transduction • multicellular organismal development • blood coagulation • positive regulation of cell proliferation • organ morphogenesis • morphogenesis of embryonic epithelium • cell differentiation • platelet activation • regulation of vascular endothelial growth factor receptor signaling pathway • positive regulation of protein autophosphorylation • response to drug • positive regulation of blood vessel endothelial cell migration • negative regulation of blood pressure • vascular endothelial growth factor receptor signaling pathway • positive regulation of epithelial cell proliferation • positive regulation of protein secretion • positive chemotaxis • induction of positive chemotaxis • positive regulation of cell division • positive regulation of mast cell chemotaxis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 4:
177.6 – 177.71 Mb

Chr 8:
55.16 – 55.27 Mb

PubMed search

[1]

[2]

Vascular endothelial growth factor C is a VEGF. The human gene encoding it is VEGFC.

The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family, is active in angiogenesis, lymphangiogenesis ^[1] and endothelial cell growth and survival, and can also affect the permeability of blood vessels. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms that bind and activate VEGFR-3 receptors. Only the fully processed form can bind and activate VEGFR-2 receptors. The structure and function of this protein is similar to those of vascular endothelial growth factor D (VEGF-D).^[2]

Pathological VEGF-C Expression

Lymphedema is caused by an imbalance between lymphatic vessel formation and absorption. Experimentally this can be created by overexpression of VEGF-C Lymphangioma: Overexpression of VEGF-C causes lymphatics to enlarge possibly facilitates metastasis.

References

Orpana A, Salven P (2003). "Angiogenic and lymphangiogenic molecules in hematological malignancies.". Leuk. Lymphoma 43 (2): 219–24. doi:10.1080/10428190290005964. PMID 11999550.
Joukov V, Pajusola K, Kaipainen A, et al. (1996). "A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.". EMBO J. 15 (7): 1751. PMC 450088. PMID 8612600. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=450088.
Joukov V, Pajusola K, Kaipainen A, et al. (1996). "A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.". EMBO J. 15 (2): 290–98. PMC 449944. PMID 8617204. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=449944.
Paavonen K, Horelli-Kuitunen N, Chilov D, et al. (1996). "Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localize to chromosomes 11q13 and 4q34, respectively.". Circulation 93 (6): 1079–82. PMID 8653826.
Lee J, Gray A, Yuan J, et al. (1996). "Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4.". Proc. Natl. Acad. Sci. U.S.A. 93 (5): 1988–92. doi:10.1073/pnas.93.5.1988. PMC 39896. PMID 8700872. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=39896.
Joukov V, Sorsa T, Kumar V, et al. (1997). "Proteolytic processing regulates receptor specificity and activity of VEGF-C.". EMBO J. 16 (13): 3898–911. doi:10.1093/emboj/16.13.3898. PMC 1170014. PMID 9233800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170014.
Fitz LJ, Morris JC, Towler P, et al. (1997). "Characterization of murine Flt4 ligand/VEGF-C.". Oncogene 15 (5): 613–8. doi:10.1038/sj.onc.1201191. PMID 9247316.
Dunk C, Ahmed A (2001). "Expression of VEGF-C and activation of its receptors VEGFR-2 and VEGFR-3 in trophoblast.". Histol. Histopathol. 16 (2): 359–75. PMID 11332691.
Dias S, Choy M, Alitalo K, Rafii S (2002). "Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy.". Blood 99 (6): 2179–84. doi:10.1182/blood.V99.6.2179. PMID 11877295.
Ueda M, Terai Y, Yamashita Y, et al. (2002). "Correlation between vascular endothelial growth factor-C expression and invasion phenotype in cervical carcinomas.". Int. J. Cancer 98 (3): 335–43. doi:10.1002/ijc.10193. PMID 11920583.
Witte D, Thomas A, Ali N, et al. (2002). "Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma.". Anticancer Res. 22 (3): 1463–6. PMID 12168824.
Schoppmann SF, Birner P, Stöckl J, et al. (2002). "Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis.". Am. J. Pathol. 161 (3): 947–56. doi:10.1016/S0002-9440(10)64255-1. PMC 1867252. PMID 12213723. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1867252.
Shin HY, Smith ML, Toy KJ, et al. (2002). "VEGF-C mediates cyclic pressure-induced endothelial cell proliferation". Physiol. Genomics 11 (3): 245–51. doi:10.1152/physiolgenomics.00068.2002. PMID 12388793.
Yu DH, Wen YM, Sun JD, et al. (2003). "[Relationship among expression of vascular endothelial growth factor-C(VEGF-C), angiogenesis, lymphangiogenesis, and lymphatic metastasis in oral cancer]". Ai Zheng 21 (3): 319–22. PMID 12452004.
Nakashima T, Kondoh S, Kitoh H, et al. (2003). "Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis". Int. J. Mol. Med. 11 (1): 33–9. PMID 12469214.
Tsai PW, Shiah SG, Lin MT, et al. (2003). "Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-kappa B signaling pathway". J. Biol. Chem. 278 (8): 5750–9. doi:10.1074/jbc.M204863200. PMID 12471041.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Masood R, Kundra A, Zhu S, et al. (2003). "Malignant mesothelioma growth inhibition by agents that target the VEGF and VEGF-C autocrine loops". Int. J. Cancer 104 (5): 603–10. doi:10.1002/ijc.10996. PMID 12594815.
Ohno M, Nakamura T, Kunimoto Y, et al. (2004). "Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer". Oncol. Rep. 10 (4): 939–43. PMID 12792749.

Growth factors

Fibroblast	FGF receptor ligands: FGF1/FGF2/FGF5 · FGF3/FGF4/FGF6 · KGF (FGF7/FGF10/FGF22) · FGF8/FGF17/FGF18 · FGF9/FGF16/FGF20 FGF homologous factors: FGF11 · FGF12 · FGF13 · FGF14 hormone-like: FGF19 · FGF21 · FGF23

EGF-like domain	TGF-α · EGF · HB-EGF

TGFβ pathway	TGF-β (TGF-β1, TGF-β2, TGF-β3)

Insulin-like	IGF-1 · IGF-2

Platelet-derived	PDGFA · PDGFB · PDGFC · PDGFD

Vascular endothelial	VEGF-A · VEGF-B · VEGF-C · VEGF-D · PGF

Other	Nerve · Hepatocyte

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

Vascular endothelial growth factor C

Pathological VEGF-C Expression

References

Further reading