VEGF-D

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VEGF-D

Existing structure data : PDB  2XV7

Properties of human protein
Mass / length primary structure 354 amino acids , 40,444 Da
Identifier
External IDs
Orthologue (human)
Entrez 2277
Ensemble ENSG00000165197
UniProt O43915
Refseq (mRNA) NM_004469.5
Refseq (protein) NP_004460.1
PubMed search 2277

Vascular Endothelial Growth Factor D (VEGF-D) is a protein that functions as a growth factor . It belongs to the group of the Platelet Derived Growth Factor / Vascular Endothelial Growth Factor (PDGF / VEGF) family. It is also known under the name c-fos-induced growth factor (FIGF) , which, however, was only used in the first publication from 1996.

Functions

VEGF-D is a growth factor that stimulates the growth of lymph vessels ( lymphangiogenesis ) and blood vessels ( angiogenesis ). Although it is very similar to VEGF-C , it does not appear to be vital - at least in mice. If the VEGF-D gene is inactivated in mice ( gene knockout ), the mice are viable and have only minimal differences from normal ( wild-type ) mice. In contrast, VEGF-C is essential (i.e. a mouse without VEGF-C is not viable).

Differences to VEGF-C

Although the biosynthesis of VEGF-D is very similar to that of VEGF-C, VEGF-D requires different enzymes in order to be activated. In contrast to VEGF-D, there is an isoform for VEGF-D that no longer has any lymphangiogenic effect (i.e. has no growth effect on lymphatic vessels) because it can no longer bind and activate the VEGF receptor-3 (VEGFR-3). This explains u. A. Presumably also why VEGF-D was identified as the strongest angiogenic factor in some experiments.

Disease relevance

Since VEGF-D can stimulate the growth of blood and lymph vessels , it is assumed that - similar to VEGF-C - it can contribute to the supply of certain tumors with blood vessels and thus to the supply of oxygen and nutrients ( tumor angiogenesis ) and to lymphatic metastasis .

discovery

VEGF-D was independently discovered and described by four different laboratories in 1996, 1997, and 1998. Although the 1998 collaborative publication of the laboratories of Kari Alitalo and Marc Achen / Steven Stacker was the last of the three publications them to the standard reference.

Individual evidence

  1. ↑ a b M Orlandini, L Marconcini, R Ferruzzi, S Oliviero: Identification of a c-fos-induced gene that is related to the platelet-derived growth factor / vascular endothelial growth factor family . In: Proceedings of the National Academy of Sciences of the United States of America . 93, No. 21, October 15, 1996, ISSN  0027-8424 , pp. 11675-11680. PMID 8876195 . PMC 38117 (free full text).
  2. ↑ Megan E. Baldwin, Michael M. Halford, Sally Roufail, Richard A. Williams, Margaret L. Hibbs, Dianne Grail, Hajime Kubo, Steven A. Stacker, Marc G. Achen: Vascular Endothelial Growth Factor D Is Dispensable for Development of the Lymphatic System . In: Molecular and Cellular Biology . 25, No. 6, March 15, 2005, ISSN  0270-7306 , pp. 2441-2449. doi : 10.1128 / MCB.25.6.2441-2449.2005 . Retrieved September 22, 2012.
  3. ↑ Marika J. Karkkainen, Paula Haiko, Kirsi Sainio, Juha Partanen, Jussi Taipale, Tatiana V. Petrova, Michael Jeltsch, David G. Jackson, Marja Talikka, Heikki Rauvala, Christer Betsholtz, Kari Alitalo: Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins . In: Nature Immunology . 5, No. 1, 2004, pp. 74-80. doi : 10.1038 / ni1013 .
  4. ↑ Steven A. Stacker, Kaye Stenvers, Carol Caesar, Angela Vitali, Teresa Domagala, Edouard Nice, Sally Roufail, Richard J. Simpson, Robert Moritz, Terhi Karpanen, Kari Alitalo, Marc G. Achen: Biosynthesis of Vascular Endothelial Growth Factor- D Involves Proteolytic Processing Which Generates Non-covalent Homodimers . In: Journal of Biological Chemistry . 274, No. 45, November 5, 1999, ISSN  0021-9258 , pp. 32127-32136. doi : 10.1074 / jbc.274.45.32127 . Retrieved September 15, 2012.
  5. ↑ Hung M. Bui, David Enis, Marius R. Robciuc, Harri J. Nurmi, Jennifer Cohen, Mei Chen, Yiqing Yang, Veerpal Dhillon, Kathy Johnson, Hong Zhang, Robert Kirkpatrick, Elizabeth Traxler, Andrey Anisimov, Kari Alitalo, Mark L. Kahn: Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD . In: The Journal of Clinical Investigation . 126, No. 6, June 1, 2016, ISSN  0021-9738 , pp. 2167-2180. doi : 10.1172 / JCI83967 . Retrieved September 19, 2016.
  6. ↑ Veli-Matti Leppanen, Michael Jeltsch, Andrey Anisimov, Denis Tvorogov, Kukka Aho, Nisse Kalkkinen, Pyry Toivanen, Seppo Ylä-Herttuala, Kurt Ballmer-Hofer, Kari Alitalo: Structural determinants of vascular endothelial growth factor-D receptor binding and specificity . In: Blood . 117, No. 5, February 3, 2011, ISSN  1528-0020 , pp. 1507-1515. doi : 10.1182 / blood-2010-08-301549 . PMID 21148085 .
  7. ↑ Tuomas T. Rissanen, Johanna E. Markkanen, Marcin Gruchala, Tommi Heikura, Antti Puranen, Mikko I. Kettunen, Ivana Kholová, Risto A. Kauppinen, Marc G. Achen, Steven A. Stacker, Kari Alitalo, Seppo Ylä-Herttuala : VEGF-D Is the Strongest Angiogenic and Lymphangiogenic Effector Among VEGFs Delivered Into Skeletal Muscle via Adenoviruses . In: Circulation Research . 92, No. 10, May 30, 2003, ISSN  0009-7330 , pp. 1098-1106. doi : 10.1161 / 01.RES.0000073584.46059.E3 . PMID 12714562 . Retrieved June 15, 2017.
  8. ^ SA Stacker, MG Achen: Emerging Roles for VEGF-D in Human Disease. In: Biomolecules. Volume 8, number 1, 01 2018, p., Doi: 10.3390 / biom8010001 , PMID 29300337 , PMC 5871970 (free full text) (review).
  9. ↑ Yoshiki Yamada, Jun-ichi Nezu, Miyuki Shimane, Yuichi Hirata: Molecular Cloning of a Novel Vascular Endothelial Growth Factor, VEGF-D . In: Genomics . 42, No. 3, June 15, 1997, ISSN  0888-7543 , pp. 483-488. doi : 10.1006 / geno.1997.4774 . Retrieved October 31, 2017.
  10. ↑ Marc G. Achen, Michael Jeltsch, Eola Kukk, Taija Mäkinen, Angela Vitali, Andrew F. Wilks, Kari Alitalo, Steven A. Stacker: Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4) . In: Proceedings of the National Academy of Sciences . 95, No. 2, January 20, 1998, ISSN  0027-8424 , pp. 548-553. Retrieved September 15, 2012.