FLT4

Fms-related tyrosine kinase 4
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4BSJ​, 4BSK​
Identifiers
Symbols	FLT4 ; FLT41; LMPH1A; PCL; VEGFR3
External IDs	OMIM: 136352 MGI: 95561 HomoloGene: 7321 ChEMBL: 1955 GeneCards: FLT4 Gene
EC number	2.7.10.1
Gene ontology Molecular function • transmembrane receptor protein tyrosine kinase activity • vascular endothelial growth factor-activated receptor activity • protein binding • ATP binding • growth factor binding • protein phosphatase binding Cellular component • extracellular region • nucleus • cytoplasm • plasma membrane • integral component of plasma membrane • receptor complex Biological process • positive regulation of protein phosphorylation • positive regulation of endothelial cell proliferation • vasculature development • lymph vessel development • lymphangiogenesis • sprouting angiogenesis • transmembrane receptor protein tyrosine kinase signaling pathway • positive regulation of cell proliferation • positive regulation of vascular endothelial growth factor production • positive regulation of endothelial cell migration • peptidyl-tyrosine phosphorylation • cellular response to vascular endothelial growth factor stimulus • vascular endothelial growth factor signaling pathway • negative regulation of apoptotic process • positive regulation of MAPK cascade • positive regulation of JNK cascade • protein autophosphorylation • vascular endothelial growth factor receptor signaling pathway • blood vessel morphogenesis • regulation of blood vessel remodeling • positive regulation of ERK1 and ERK2 cascade • positive regulation of protein kinase C signaling Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2324	14257
Ensembl	ENSG00000037280	ENSMUSG00000020357
UniProt	P35916	P35917
RefSeq (mRNA)	NM_002020	NM_008029
RefSeq (protein)	NP_002011	NP_032055
Location (UCSC)	Chr 5: 180.6 – 180.65 Mb	Chr 11: 49.61 – 49.65 Mb
PubMed search

Fms-related tyrosine kinase 4, also known as FLT4, is a protein which in humans is encoded by the FLT4 gene.^[1][2]

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.^[1]

Interactions

FLT4 has been shown to interact with SHC1.^[3][4][5]

See also

• VEGF receptors

References

1. "Entrez Gene: FLT4 fms-related tyrosine kinase 4".
2. 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.
3. 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 (ENGLAND) 9 (12): 3545–55. ISSN 0950-9232. PMID 7970715.
4. Fournier, E; Blaikie P; Rosnet O; Margolis B; Birnbaum D; Borg J P (January 1999). "Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF receptor 3 signaling". Oncogene (ENGLAND) 18 (2): 507–14. doi:10.1038/sj.onc.1202315. ISSN 0950-9232. PMID 9927207.
5. Fournier, E; Rosnet O; Marchetto S; Turck C W; Rottapel R; Pelicci P G; Birnbaum D; Borg J P (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". J. Biol. Chem. (UNITED STATES) 271 (22): 12956–63. doi:10.1074/jbc.271.22.12956. ISSN 0021-9258. PMID 8662748.

External links

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

Further reading

• Petrova TV, Makinen T, Alitalo K (1999). "Signaling via vascular endothelial growth factor receptors.". Exp. Cell Res. 253 (1): 117–30. doi:10.1006/excr.1999.4707. PMID 10579917.
• Aprelikova O, Pajusola K, Partanen J; et al. (1992). "FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter.". Cancer Res. 52 (3): 746–8. PMID 1310071.
• Galland F, Karamysheva A, Mattei MG; et al. (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; et al. (1992). "FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines.". Cancer Res. 52 (20): 5738–43. PMID 1327515.
• Fournier E, Dubreuil P, Birnbaum D, Borg JP (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; et al. (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; et al. (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; et al. (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; et al. (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.". J. Biol. Chem. 271 (22): 12956–63. doi:10.1074/jbc.271.22.12956. PMID 8662748.
• 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.
• Kukk E, Lymboussaki A, Taira S; et al. (1997). "VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development.". Development 122 (12): 3829–37. PMID 9012504.
• Achen MG, Jeltsch M, Kukk E; et al. (1998). "Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4).". Proc. Natl. Acad. Sci. U.S.A. 95 (2): 548–53. doi:10.1073/pnas.95.2.548. PMC 18457. PMID 9435229.
• Ferrell RE, Levinson KL, Esman JH; et al. (1999). "Hereditary lymphedema: evidence for linkage and genetic heterogeneity.". Hum. Mol. Genet. 7 (13): 2073–8. doi:10.1093/hmg/7.13.2073. PMID 9817924.
• Fournier E, Blaikie P, Rosnet O; et al. (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; et al. (2000). "Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema.". Nat. Genet. 25 (2): 153–9. doi:10.1038/75997. PMID 10835628.
• Irrthum A, Karkkainen MJ, Devriendt K; et al. (2000). "Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase.". Am. J. Hum. Genet. 67 (2): 295–301. doi:10.1086/303019. PMC 1287178. PMID 10856194.
• Wang JF, Zhang XF, Groopman JE (2001). "Stimulation of beta 1 integrin induces tyrosine phosphorylation of vascular endothelial growth factor receptor-3 and modulates cell migration.". J. Biol. Chem. 276 (45): 41950–7. doi:10.1074/jbc.M101370200. PMID 11553610.
• Baldwin ME, Roufail S, Halford MM; et al. (2001). "Multiple forms of mouse vascular endothelial growth factor-D are generated by RNA splicing and proteolysis.". J. Biol. Chem. 276 (47): 44307–14. doi:10.1074/jbc.M106188200. PMID 11574540.
• Walter JW, North PE, Waner M; et al. (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.

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