VEGFR1 explained

Vascular endothelial growth factor receptor 1 is a protein that in humans is encoded by the FLT1 gene.^[1]

Function

FLT1 is a member of VEGF receptor gene family. It encodes a receptor tyrosine kinase which is activated by VEGF-A, VEGF-B, and placental growth factor. The sequence structure of the FLT1 gene resembles that of the FMS (now CSF1R) gene; hence, Yoshida et al. (1987) proposed the name FLT as an acronym for FMS-like tyrosine kinase.^[2]

The ablation of VEGFR1 by chemical and genetic means has also recently been found to augment the conversion of white adipose tissue to brown adipose tissue as well as increase brown adipose angiogenesis in mice.^[3]

Functional genetic variation in FLT1 (rs9582036) has been found to affect non-small cell lung cancer survival.^[4]

Interactions

FLT1 has been shown to interact with PLCG1^[5] and vascular endothelial growth factor B (VEGF-B).^{[6] [7]}

See also

• VEGF receptors

Further reading

• Petrova TV, Makinen T, Alitalo K . Signaling via vascular endothelial growth factor receptors . Experimental Cell Research . 253 . 1 . 117–30 . November 1999 . 10579917 . 10.1006/excr.1999.4707 .
• Sato Y, Kanno S, Oda N, Abe M, Ito M, Shitara K, Shibuya M . Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction . Annals of the New York Academy of Sciences . 902 . 1 . 201–5; discussion 205–7 . May 2000 . 10865839 . 10.1111/j.1749-6632.2000.tb06314.x . 11488629 .
• Boyd AW, Lackmann M . Signals from Eph and ephrin proteins: a developmental tool kit . Science's STKE . 2001 . 112 . re20 . December 2001 . 11741094 . 10.1126/stke.2001.112.re20 . 2952319 .
• Luttun A, Tjwa M, Carmeliet P . Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders . Annals of the New York Academy of Sciences . 979 . 80–93 . December 2002 . 12543719 . 10.1111/j.1749-6632.2002.tb04870.x . 73356935 .
• Maynard SE, Venkatesha S, Thadhani R, Karumanchi SA . Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia . Pediatric Research . 57 . 5 Pt 2 . 1R–7R . May 2005 . 15817508 . 10.1203/01.PDR.0000159567.85157.B7 . free .
• Shibuya M . Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis . Angiogenesis . 9 . 4 . 225–30; discussion 231 . 2007 . 17109193 . 10.1007/s10456-006-9055-8 . 20495537 .
• Widmer M, Villar J, Benigni A, Conde-Agudelo A, Karumanchi SA, Lindheimer M . Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review . Obstetrics and Gynecology . 109 . 1 . 168–80 . January 2007 . 17197602 . 10.1097/01.AOG.0000249609.04831.7c . 24187545 .
• López-Novoa JM . Soluble endoglin is an accurate predictor and a pathogenic molecule in pre-eclampsia . Nephrology, Dialysis, Transplantation . 22 . 3 . 712–4 . March 2007 . 17210583 . 10.1093/ndt/gfl768 . free .
• Poesen K, Lambrechts D, Van Damme P, Dhondt J, Bender F, Frank N, Bogaert E, Claes B, Heylen L, Verheyen A, Raes K, Tjwa M, Eriksson U, Shibuya M, Nuydens R, Van Den Bosch L, Meert T, D'Hooge R, Sendtner M, Robberecht W, Carmeliet P . Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration . The Journal of Neuroscience . 28 . 42 . 10451–9 . October 2008 . 18923022 . 10.1523/JNEUROSCI.1092-08.2008 . 6671326 . free .
• Joukov V, Kaipainen A, Jeltsch M, Pajusola K, Olofsson B, Kumar V, Eriksson U, Alitalo K . Vascular endothelial growth factors VEGF-B and VEGF-C . Journal of Cellular Physiology . 173 . 2 . 211–5 . November 1997 . 9365524 . 10.1002/(SICI)1097-4652(199711)173:2<211::AID-JCP23>3.0.CO;2-H . 2930599 .
• Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D . VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche . Nature . 438 . 7069 . 820–7 . December 2005 . 16341007 . 2945882 . 10.1038/nature04186 . 2005Natur.438..820K .

Notes and References

1. Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M . Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family . Oncogene . 5 . 4 . 519–24 . April 1990 . 2158038 .
2. Web site: FLT1 fms related receptor tyrosine kinase 1 [Homo sapiens (human) ] ]. National Center for Biotechnology Information.
3. Seki T, Hosaka K, Fischer C, Lim S, Andersson P, Abe M, Iwamoto H, Gao Y, Wang X, Fong GH, Cao Y . Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning . The Journal of Experimental Medicine . 215 . 2 . 611–626 . February 2018 . 29305395 . 5789413 . 10.1084/jem.20171012 .
4. Glubb DM, Paré-Brunet L, Jantus-Lewintre E, Jiang C, Crona D, Etheridge AS, Mirza O, Zhang W, Seiser EL, Rzyman W, Jassem J, Auman T, Hirsch FR, Owzar K, Camps C, Dziadziuszko R, Innocenti F . Functional FLT1 Genetic Variation is a Prognostic Factor for Recurrence in Stage I-III Non-Small-Cell Lung Cancer . Journal of Thoracic Oncology . 10 . 7 . 1067–75 . July 2015 . 26134224 . 4494119 . 10.1097/JTO.0000000000000549 .
5. Cunningham SA, Arrate MP, Brock TA, Waxham MN . Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites . Biochemical and Biophysical Research Communications . 240 . 3 . 635–9 . November 1997 . 9398617 . 10.1006/bbrc.1997.7719 .
6. Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U . Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells . Proceedings of the National Academy of Sciences of the United States of America . 95 . 20 . 11709–14 . September 1998 . 9751730 . 21705 . 10.1073/pnas.95.20.11709 . free .
7. Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K . Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1 . The Journal of Biological Chemistry . 274 . 30 . 21217–22 . July 1999 . 10409677 . 10.1074/jbc.274.30.21217 . free .