VEGFR1

Vascular endothelial growth factor receptor 1 is a protein that in humans is encoded by the FLT1 gene.^[5]

FLT1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1FLT, 1QSV, 1QSZ, 1QTY, 1RV6, 2XAC, 3HNG, 4CKV, 4CL7, 5EX3
Identifiers
Aliases	FLT1, FLT, FLT-1, VEGFR-1, VEGFR1, fms related tyrosine kinase 1, vascular endothelial growth factor receptor 1, fms related receptor tyrosine kinase 1
External IDs	OMIM: 165070; MGI: 95558; HomoloGene: 134179; GeneCards: FLT1; OMA:FLT1 - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q12.3 Start 28,300,346 bp[1] End 28,495,145 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 G3|5 87.01 cM Start 147,498,414 bp[2] End 147,662,821 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pericardium placenta endothelial cell right ventricle myocardium of left ventricle dorsal motor nucleus of vagus nerve cardia thyroid gland left lobe of thyroid gland internal globus pallidus Top expressed in right lung right lung lobe internal carotid artery myocardium of ventricle muscle of thigh external carotid artery umbilical cord cardiac muscle tissue of left ventricle islet of Langerhans substantia nigra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function vascular endothelial growth factor-activated receptor activity transferase activity nucleotide binding protein kinase activity placental growth factor-activated receptor activity kinase activity protein binding transmembrane receptor protein tyrosine kinase activity protein tyrosine kinase activity ATP binding growth factor binding vascular endothelial growth factor binding Cellular component cytoplasm integral component of membrane endosome focal adhesion membrane receptor complex integral component of plasma membrane extracellular region extracellular space plasma membrane actin cytoskeleton Biological process positive regulation of vascular endothelial growth factor receptor signaling pathway cell differentiation blood vessel morphogenesis vascular endothelial growth factor receptor-1 signaling pathway positive regulation of MAP kinase activity monocyte chemotaxis positive regulation of phospholipase C activity transmembrane receptor protein tyrosine kinase signaling pathway vascular endothelial growth factor signaling pathway phosphorylation positive regulation of angiogenesis positive regulation of phosphatidylinositol 3-kinase activity multicellular organism development chemotaxis protein phosphorylation vascular endothelial growth factor receptor signaling pathway embryonic morphogenesis angiogenesis protein autophosphorylation positive regulation of phosphatidylinositol 3-kinase signaling peptidyl-tyrosine phosphorylation cellular response to vascular endothelial growth factor stimulus cell migration positive regulation of MAPK cascade positive regulation of cell population proliferation positive regulation of cell migration sprouting angiogenesis positive regulation of ERK1 and ERK2 cascade negative regulation of vascular endothelial cell proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2321 14254 Ensembl ENSG00000102755 ENSMUSG00000029648 UniProt P17948 P35969 RefSeq (mRNA) NM_001159920 NM_001160030 NM_001160031 NM_002019 NM_010228 NM_001363135 RefSeq (protein) NP_001153392 NP_001153502 NP_001153503 NP_002010 NP_034358 NP_001350064 Location (UCSC) Chr 13: 28.3 – 28.5 Mb Chr 5: 147.5 – 147.66 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[6]

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.^[7]

Functional genetic variation in FLT1 (rs9582036) has been found to affect non-small cell lung cancer survival.^[8]

Interactions

FLT1 has been shown to interact with PLCG1^[9] and vascular endothelial growth factor B (VEGF-B).^[10][11]

See also

• VEGF receptors

References

1. GRCh38: Ensembl release 89: ENSG00000102755 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029648 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M (April 1990). "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. PMID 2158038.
6. "FLT1 fms related receptor tyrosine kinase 1 [ Homo sapiens (human) ]". National Center for Biotechnology Information.
7. Seki T, Hosaka K, Fischer C, Lim S, Andersson P, Abe M, Iwamoto H, Gao Y, Wang X, Fong GH, Cao Y (February 2018). "Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning". The Journal of Experimental Medicine. 215 (2): 611–626. doi:10.1084/jem.20171012. PMC 5789413. PMID 29305395.
8. 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 (July 2015). "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. doi:10.1097/JTO.0000000000000549. PMC 4494119. PMID 26134224.
9. Cunningham SA, Arrate MP, Brock TA, Waxham MN (November 1997). "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. doi:10.1006/bbrc.1997.7719. PMID 9398617.
10. Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U (September 1998). "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. doi:10.1073/pnas.95.20.11709. PMC 21705. PMID 9751730.
11. Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K (July 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry. 274 (30): 21217–22. doi:10.1074/jbc.274.30.21217. PMID 10409677.

Further reading

• Petrova TV, Makinen T, Alitalo K (November 1999). "Signaling via vascular endothelial growth factor receptors". Experimental Cell Research. 253 (1): 117–30. doi:10.1006/excr.1999.4707. PMID 10579917.
• Sato Y, Kanno S, Oda N, Abe M, Ito M, Shitara K, Shibuya M (May 2000). "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. doi:10.1111/j.1749-6632.2000.tb06314.x. PMID 10865839. S2CID 11488629.
• Boyd AW, Lackmann M (December 2001). "Signals from Eph and ephrin proteins: a developmental tool kit". Science's STKE. 2001 (112): re20. doi:10.1126/stke.2001.112.re20. PMID 11741094. S2CID 2952319.
• Luttun A, Tjwa M, Carmeliet P (December 2002). "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. doi:10.1111/j.1749-6632.2002.tb04870.x. PMID 12543719. S2CID 73356935.
• Maynard SE, Venkatesha S, Thadhani R, Karumanchi SA (May 2005). "Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia". Pediatric Research. 57 (5 Pt 2): 1R–7R. doi:10.1203/01.PDR.0000159567.85157.B7. PMID 15817508.
• Shibuya M (2007). "Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis". Angiogenesis. 9 (4): 225–30, discussion 231. doi:10.1007/s10456-006-9055-8. PMID 17109193. S2CID 20495537.
• Widmer M, Villar J, Benigni A, Conde-Agudelo A, Karumanchi SA, Lindheimer M (January 2007). "Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review". Obstetrics and Gynecology. 109 (1): 168–80. doi:10.1097/01.AOG.0000249609.04831.7c. PMID 17197602. S2CID 24187545.
• López-Novoa JM (March 2007). "Soluble endoglin is an accurate predictor and a pathogenic molecule in pre-eclampsia". Nephrology, Dialysis, Transplantation. 22 (3): 712–4. doi:10.1093/ndt/gfl768. PMID 17210583.
• 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 (October 2008). "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. doi:10.1523/JNEUROSCI.1092-08.2008. PMC 6671326. PMID 18923022.
• Joukov V, Kaipainen A, Jeltsch M, Pajusola K, Olofsson B, Kumar V, Eriksson U, Alitalo K (November 1997). "Vascular endothelial growth factors VEGF-B and VEGF-C". Journal of Cellular Physiology. 173 (2): 211–5. doi:10.1002/(SICI)1097-4652(199711)173:2<211::AID-JCP23>3.0.CO;2-H. PMID 9365524. S2CID 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 (December 2005). "VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche". Nature. 438 (7069): 820–7. Bibcode:2005Natur.438..820K. doi:10.1038/nature04186. PMC 2945882. PMID 16341007.