FLT4

Fms-related tyrosine kinase 4, also known as FLT4, is a protein which in humans is encoded by the FLT4 gene.

FLT4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4BSJ, 4BSK
Identifiers
Aliases	FLT4, FLT41, LMPH1A, PCL, VEGFR3, FLT-4, VEGFR-3, fms related tyrosine kinase 4, LMPHM1, fms related receptor tyrosine kinase 4, CHTD7
External IDs	OMIM: 136352; MGI: 95561; HomoloGene: 7321; GeneCards: FLT4; OMA:FLT4 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q35.3 Start 180,601,506 bp End 180,649,624 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B1.2|11 29.69 cM Start 49,500,090 bp End 49,543,566 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland left lobe of thyroid gland apex of heart right lung upper lobe of left lung sural nerve spleen right uterine tube left uterine tube body of uterus Top expressed in endothelial cell of lymphatic vessel internal carotid artery left lobe of liver decidua external carotid artery mesenteric lymph nodes left lung left lung lobe right lung aortic valve More reference expression data BioGPS n/a
Gene ontology Molecular function vascular endothelial growth factor-activated receptor activity transferase activity nucleotide binding protein kinase activity growth factor binding kinase activity protein binding transmembrane receptor protein tyrosine kinase activity protein tyrosine kinase activity protein phosphatase binding ATP binding protein homodimerization activity receptor tyrosine kinase transmembrane signaling receptor activity vascular endothelial growth factor binding Cellular component cytoplasm integral component of membrane membrane receptor complex plasma membrane integral component of plasma membrane extracellular region nucleus nucleoplasm Biological process regulation of blood vessel remodeling positive regulation of protein phosphorylation positive regulation of endothelial cell proliferation blood vessel morphogenesis lymphangiogenesis phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway positive regulation of protein kinase C signaling negative regulation of apoptotic process sprouting angiogenesis positive regulation of JNK cascade lymph vessel development positive regulation of endothelial cell migration protein phosphorylation vascular endothelial growth factor receptor signaling pathway vasculature development angiogenesis positive regulation of cell population proliferation positive regulation of ERK1 and ERK2 cascade protein autophosphorylation positive regulation of vascular endothelial growth factor production peptidyl-tyrosine phosphorylation cellular response to vascular endothelial growth factor stimulus positive regulation of MAPK cascade lung alveolus development respiratory system process respiratory gaseous exchange by respiratory system vascular endothelial growth factor signaling pathway negative regulation of signal transduction cell differentiation positive regulation of phosphatidylinositol 3-kinase signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2324 14257 Ensembl ENSG00000037280 ENSMUSG00000020357 UniProt P35916 P35917 RefSeq (mRNA) NM_002020 NM_182925 NM_001354989 NM_008029 RefSeq (protein) NP_002011 NP_891555 NP_001341918 NP_032055 Location (UCSC) Chr 5: 180.6 – 180.65 Mb Chr 11: 49.5 – 49.54 Mb PubMed search
Wikidata
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This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA.

Interactions

FLT4 has been shown to interact with SHC1.

See also

• VEGF receptors

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.
• Aprelikova O, Pajusola K, Partanen J, Armstrong E, Alitalo R, Bailey SK, McMahon J, Wasmuth J, Huebner K, Alitalo K (February 1992). "FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter". Cancer Research. 52 (3): 746–8. PMID 1310071.
• Galland F, Karamysheva A, Mattei MG, Rosnet O, Marchetto S, Birnbaum D (June 1992). "Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene". Genomics. 13 (2): 475–8. doi:10.1016/0888-7543(92)90277-Y. PMID 1319394.
• Pajusola K, Aprelikova O, Korhonen J, Kaipainen A, Pertovaara L, Alitalo R, Alitalo K (October 1992). "FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines". Cancer Research. 52 (20): 5738–43. PMID 1327515.
• Fournier E, Dubreuil P, Birnbaum D, Borg JP (September 1995). "Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor". Oncogene. 11 (5): 921–31. PMID 7675451.
• Pajusola K, Aprelikova O, Armstrong E, Morris S, Alitalo K (November 1993). "Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts". Oncogene. 8 (11): 2931–7. PMID 7692369.
• Pajusola K, Aprelikova O, Pelicci G, Weich H, Claesson-Welsh L, Alitalo K (December 1994). "Signalling properties of FLT4, a proteolytically processed receptor tyrosine kinase related to two VEGF receptors". Oncogene. 9 (12): 3545–55. PMID 7970715.
• Galland F, Karamysheva A, Pebusque MJ, Borg JP, Rottapel R, Dubreuil P, Rosnet O, Birnbaum D (May 1993). "The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor". Oncogene. 8 (5): 1233–40. PMID 8386825.
• Fournier E, Rosnet O, Marchetto S, Turck CW, Rottapel R, Pelicci PG, Birnbaum D, Borg JP (May 1996). "Interaction with the phosphotyrosine binding domain/phosphotyrosine interacting domain of SHC is required for the transforming activity of the FLT4/VEGFR3 receptor tyrosine kinase". The Journal of Biological Chemistry. 271 (22): 12956–63. doi:10.1074/jbc.271.22.12956. PMID 8662748.
• Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI (March 1996). "Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4". Proceedings of the National Academy of Sciences of the United States of America. 93 (5): 1988–92. Bibcode:1996PNAS...93.1988L. doi:10.1073/pnas.93.5.1988. PMC 39896. PMID 8700872.
• Kukk E, Lymboussaki A, Taira S, Kaipainen A, Jeltsch M, Joukov V, Alitalo K (December 1996). "VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development". Development. 122 (12): 3829–37. doi:10.1242/dev.122.12.3829. PMID 9012504.
• Achen MG, Jeltsch M, Kukk E, Mäkinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA (January 1998). "Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4)". Proceedings of the National Academy of Sciences of the United States of America. 95 (2): 548–53. Bibcode:1998PNAS...95..548A. doi:10.1073/pnas.95.2.548. PMC 18457. PMID 9435229.
• Ferrell RE, Levinson KL, Esman JH, Kimak MA, Lawrence EC, Barmada MM, Finegold DN (December 1998). "Hereditary lymphedema: evidence for linkage and genetic heterogeneity". Human Molecular Genetics. 7 (13): 2073–8. doi:10.1093/hmg/7.13.2073. PMID 9817924.
• Fournier E, Blaikie P, Rosnet O, Margolis B, Birnbaum D, Borg JP (January 1999). "Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF receptor 3 signaling". Oncogene. 18 (2): 507–14. doi:10.1038/sj.onc.1202315. PMID 9927207.
• Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA, Alitalo K, Finegold DN (June 2000). "Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema". Nature Genetics. 25 (2): 153–9. doi:10.1038/75997. PMID 10835628. S2CID 38445644.
• Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M (August 2000). "Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase". American Journal of Human Genetics. 67 (2): 295–301. doi:10.1086/303019. PMC 1287178. PMID 10856194.
• Wang JF, Zhang XF, Groopman JE (November 2001). "Stimulation of beta 1 integrin induces tyrosine phosphorylation of vascular endothelial growth factor receptor-3 and modulates cell migration". The Journal of Biological Chemistry. 276 (45): 41950–7. doi:10.1074/jbc.M101370200. PMID 11553610.
• Baldwin ME, Roufail S, Halford MM, Alitalo K, Stacker SA, Achen MG (November 2001). "Multiple forms of mouse vascular endothelial growth factor-D are generated by RNA splicing and proteolysis". The Journal of Biological Chemistry. 276 (47): 44307–14. doi:10.1074/jbc.M106188200. PMID 11574540.
• Walter JW, North PE, Waner M, Mizeracki A, Blei F, Walker JW, Reinisch JF, Marchuk DA (March 2002). "Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma". Genes, Chromosomes & Cancer. 33 (3): 295–303. doi:10.1002/gcc.10028. PMID 11807987. S2CID 33428561.

External links

• GeneReviews/NCBI/NIH/UW entry on Milroy Disease

This article incorporates text from the United States National Library of Medicine, which is in the public domain.