NameVascular endothelial growth factor receptor 3
Synonyms
  • 2.7.10.1
  • FLT-4
  • Fms-like tyrosine kinase 4
  • Tyrosine-protein kinase receptor FLT4
  • VEGFR-3
  • VEGFR3
Gene NameFLT4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0036936|Vascular endothelial growth factor receptor 3
MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWA
WPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARI
EGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDG
QEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNELYDIQLLPRKSL
ELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNV
SQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAA
YPPPEFQWYKDGKALSGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNV
PPQIHEKEASSPSIYSRHSRQALTCTAYGVPLPLSIQWHWRPWTPCKMFAQRSLRRRQQQ
DLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQNANVSAMYKCVVSNKV
GQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHD
AHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRS
HDKHCHKKYLSVQALEAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEE
KSGVDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAVEGSEDKGSMEIVILV
GTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLEEQCEYLSYDASQWEF
PRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKIL
IHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRF
RAMVELARLDRRRPGSSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQ
VARGMEFLASRKCIHRDLAARNILLSESDVVKICDFGLARDIYKDPDYVRKGSARLPLKW
MAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLRDGTRMRAPELA
TPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFS
QVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPM
TPTTYKGSVDNQTDSGMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRR
RPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY
Number of residues1363
Molecular Weight152755.94
Theoretical pI6.24
GO Classification
Functions
  • growth factor binding
  • ATP binding
  • transmembrane receptor protein tyrosine kinase activity
  • protein phosphatase binding
  • vascular endothelial growth factor-activated receptor activity
Processes
  • lymph vessel development
  • lymphangiogenesis
  • peptidyl-tyrosine phosphorylation
  • positive regulation of JNK cascade
  • positive regulation of protein phosphorylation
  • positive regulation of MAPK cascade
  • positive regulation of protein kinase C signaling
  • negative regulation of apoptotic process
  • regulation of blood vessel remodeling
  • vascular endothelial growth factor receptor signaling pathway
  • sprouting angiogenesis
  • positive regulation of cell proliferation
  • vascular endothelial growth factor signaling pathway
  • positive regulation of endothelial cell migration
  • vasculature development
  • positive regulation of ERK1 and ERK2 cascade
  • protein autophosphorylation
  • positive regulation of vascular endothelial growth factor production
  • transmembrane receptor protein tyrosine kinase signaling pathway
  • positive regulation of endothelial cell proliferation
  • blood vessel morphogenesis
  • cellular response to vascular endothelial growth factor stimulus
Components
  • integral component of plasma membrane
  • cytoplasm
  • extracellular region
  • nucleus
  • plasma membrane
  • receptor complex
General FunctionVascular endothelial growth factor-activated receptor activity
Specific FunctionTyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.
Pfam Domain Function
Transmembrane Regions776-796
GenBank Protein ID297050
UniProtKB IDP35916
UniProtKB Entry NameVGFR3_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0010134|Vascular endothelial growth factor receptor 3 (FLT4)
ATGCAGCGGGGCGCCGCGCTGTGCCTGCGACTGTGGCTCTGCCTGGGACTCCTGGACGGC
CTGGTGAGTGGCTACTCCATGACCCCCCCGACCTTGAACATCACGGAGGAGTCACACGTC
ATCGACACCGGTGACAGCCTGTCCATCTCCTGCAGGGGACAGCACCCCCTCGAGTGGGCT
TGGCCAGGAGCTCAGGAGGCGCCAGCCACCGGAGACAAGGACAGCGAGGACACGGGGGTG
GTGCGAGACTGCGAGGGCACAGACGCCAGGCCCTACTGCAAGGTGTTGCTGCTGCACGAG
GTACATGCCAACGACACAGGCAGCTACGTCTGCTACTACAAGTACATCAAGGCACGCATC
GAGGGCACCACGGCCGCCAGCTCCTACGTGTTCGTGAGAGACTTTGAGCAGCCATTCATC
AACAAGCCTGACACGCTCTTGGTCAACAGGAAGGACGCCATGTGGGTGCCCTGTCTGGTG
TCCATCCCCGGCCTCAATGTCACGCTGCGCTCGCAAAGCTCGGTGCTGTGGCCAGACGGG
CAGGAGGTGGTGTGGGATGACCGGCGGGGCATGCTCGTGTCCACGCCACTGCTGCACGAT
GCCCTGTACCTGCAGTGCGAGACCACCTGGGGAGACCAGGACTTCCTTTCCAACCCCTTC
CTGGTGCACATCACAGGCAACGAGCTCTATGACATCCAGCTGTTGCCCAGGAAGTCGCTG
GAGCTGCTGGTAGGGGAGAAGCTGGTCCTGAACTGCACCGTGTGGGCTGAGTTTAACTCA
GGTGTCACCTTTGACTGGGACTACCCAGGGAAGCAGGCAGAGCGGGGTAAGTGGGTGCCC
GAGCGACGCTCCCAGCAGACCCACACAGAACTCTCCAGCATCCTGACCATCCACAACGTC
AGCCAGCACGACCTGGGCTCGTATGTGTGCAAGGCCAACAACGGCATCCAGCGATTTCGG
GAGAGCACCGAGGTCATTGTGCATGAAAATCCCTTCATCAGCGTCGAGTGGCTCAAAGGA
CCCATCCTGGAGGCCACGGCAGGAGACGAGCTGGTGAAGCTGCCCGTGAAGCTGGCAGCG
TACCCCCCGCCCGAGTTCCAGTGGTACAAGGATGGAAAGGCACTGTCCGGGCGCCACAGT
CCACATGCCCTGGTGCTCAAGGAGGTGACAGAGGCCAGCACAGGCACCTACACCCTCGCC
CTGTGGAACTCCGCTGCTGGCCTGAGGCGCAACATCAGCCTGGAGCTGGTGGTGAATGTG
CCCCCCCAGATACATGAGAAGGAGGCCTCCTCCCCCAGCATCTACTCGCGTCACAGCCGC
CAGGCCCTCACCTGCACGGCCTACGGGGTGCCCCTGCCTCTCAGCATCCAGTGGCACTGG
CGGCCCTGGACACCCTGCAAGATGTTTGCCCAGCGTAGTCTCCGGCGGCGGCAGCAGCAA
GACCTCATGCCACAGTGCCGTGACTGGAGGGCGGTGACCACGCAGGATGCCGTGAACCCC
ATCGAGAGCCTGGACACCTGGACCGAGTTTGTGGAGGGAAAGAATAAGACTGTGAGCAAG
CTGGTGATCCAGAATGCCAACGTGTCTGCCATGTACAAGTGTGTGGTCTCCAACAAGGTG
GGCCAGGATGAGCGGCTCATCTACTTCTATGTGACCACCATCCCCGACGGCTTCACCATC
GAATCCAAGCCATCCGAGGAGCTACTAGAGGGCCAGCCGGTGCTCCTGAGCTGCCAAGCC
GACAGCTACAAGTACGAGCATCTGCGCTGGTACCGCCTCAACCTGTCCACGCTGCACGAT
GCGCACGGGAACCCGCTTCTGCTCGACTGCAAGAACGTGCATCTGTTCGCCACCCCTCTG
GCCGCCAGCCTGGAGGAGGTGGCACCTGGGGCGCGCCACGCCACGCTCAGCCTGAGTATC
CCCCGCGTCGCGCCCGAGCACGAGGGCCACTATGTGTGCGAAGTGCAAGACCGGCGCAGC
CATGACAAGCACTGCCACAAGAAGTACCTGTCGGTGCAGGCCCTGGAAGCCCCTCGGCTC
ACGCAGAACTTGACCGACCTCCTGGTGAACGTGAGCGACTCGCTGGAGATGCAGTGCTTG
GTGGCCGGAGCGCACGCGCCCAGCATCGTGTGGTACAAAGACGAGAGGCTGCTGGAGGAA
AAGTCTGGAGTCGACTTGGCGGACTCCAACCAGAAGCTGAGCATCCAGCGCGTGCGCGAG
GAGGATGCGGGACGCTATCTGTGCAGCGTGTGCAACGCCAAGGGCTGCGTCAACTCCTCC
GCCAGCGTGGCCGTGGAAGGCTCCGAGGATAAGGGCAGCATGGAGATCGTGATCCTTGTC
GGTACCGGCGTCATCGCTGTCTTCTTCTGGGTCCTCCTCCTCCTCATCTTCTGTAACATG
AGGAGGCCGGCCCACGCAGACATCAAGACGGGCTACCTGTCCATCATCATGGACCCCGGG
GAGGTGCCTCTGGAGGAGCAATGCGAATACCTGTCCTACGATGCCAGCCAGTGGGAATTC
CCCCGAGAGCGGCTGCACCTGGGGAGAGTGCTCGGCTACGGCGCCTTCGGGAAGGTGGTG
GAAGCCTCCGCTTTCGGCATCCACAAGGGCAGCAGCTGTGACACCGTGGCCGTGAAAATG
CTGAAAGAGGGCGCCACGGCCAGCGAGCACCGCGCGCTGATGTCGGAGCTCAAGATCCTC
ATTCACATCGGCAACCACCTCAACGTGGTCAACCTCCTCGGGGCGTGCACCAAGCCGCAG
GGCCCCCTCATGGTGATCGTGGAGTTCTGCAAGTACGGCAACCTCTCCAACTTCCTGCGC
GCCAAGCGGGACGCCTTCAGCCCCTGCGCGGAGAAGTCTCCCGAGCAGCGCGGACGCTTC
CGCGCCATGGTGGAGCTCGCCAGGCTGGATCGGAGGCGGCCGGGGAGCAGCGACAGGGTC
CTCTTCGCGCGGTTCTCGAAGACCGAGGGCGGAGCGAGGCGGGCTTCTCCAGACCAAGAA
GCTGAGGACCTGTGGCTGAGCCCGCTGACCATGGAAGATCTTGTCTGCTACAGCTTCCAG
GTGGCCAGAGGGATGGAGTTCCTGGCTTCCCGAAAGTGCATCCACAGAGACCTGGCTGCT
CGGAACATTCTGCTGTCGGAAAGCGACGTGGTGAAGATCTGTGACTTTGGCCTTGCCCGG
GACATCTACAAAGACCCCGACTACGTCCGCAAGGGCAGTGCCCGGCTGCCCCTGAAGTGG
ATGGCCCCTGAAAGCATCTTCGACAAGGTGTACACCACGCAGAGTGACGTGTGGTCCTTT
GGGGTGCTTCTCTGGGAGATCTTCTCTCTGGGGGCCTCCCCGTACCCTGGGGTGCAGATC
AATGAGGAGTTCTGCCAGCGGCTGAGAGACGGCACAAGGATGAGGGCCCCGGAGCTGGCC
ACTCCCGCCATACGCCGCATCATGCTGAACTGCTGGTCCGGAGACCCCAAGGCGAGACCT
GCATTCTCGGAGCTGGTGGAGATCCTGGGGGACCTGCTCCAGGGCAGGGGCCTGCAAGAG
GAAGAGGAGGTCTGCATGGCCCCGCGCAGCTCTCAGAGCTCAGAAGAGGGCAGCTTCTCG
CAGGTGTCCACCATGGCCCTACACATCGCCCAGGCTGACGCTGAGGACAGCCCGCCAAGC
CTGCAGCGCCACAGCCTGGCCGCCAGGTATTACAACTGGGTGTCCTTTCCCGGGTGCCTG
GCCAGAGGGGCTGAGACCCGTGGTTCCTCCAGGATGAAGACATTTGAGGAATTCCCCATG
ACCCCAACGACCTACAAAGGCTCTGTGGACAACCAGACAGACAGTGGGATGGTGCTGGCC
TCGGAGGAGTTTGAGCAGATAGAGAGCAGGCATAGACAAGAAAGCGGCTTCAGGTAG
GenBank Gene IDX69878
GeneCard IDNot Available
GenAtlas IDFLT4
HGNC IDHGNC:3767
Chromosome Location5
Locus5q35.3
References
  1. Pajusola K, Aprelikova O, Korhonen J, Kaipainen A, Pertovaara L, Alitalo R, Alitalo K: FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res. 1992 Oct 15;52(20):5738-43. 1327515
  2. Galland F, Karamysheva A, Mattei MG, Rosnet O, Marchetto S, Birnbaum D: Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene. Genomics. 1992 Jun;13(2):475-8. 1319394
  3. Galland F, Karamysheva A, Pebusque MJ, Borg JP, Rottapel R, Dubreuil P, Rosnet O, Birnbaum D: The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor. Oncogene. 1993 May;8(5):1233-40. 8386825
  4. Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI: Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1988-92. 8700872
  5. Jin P, Zhang J, Sumariwalla PF, Ni I, Jorgensen B, Crawford D, Phillips S, Feldmann M, Shepard HM, Paleolog EM: Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res Ther. 2008;10(4):R73. doi: 10.1186/ar2447. Epub 2008 Jul 1. 18593464
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. 15372022
  8. Aprelikova O, Pajusola K, Partanen J, Armstrong E, Alitalo R, Bailey SK, McMahon J, Wasmuth J, Huebner K, Alitalo K: FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter. Cancer Res. 1992 Feb 1;52(3):746-8. 1310071
  9. Pajusola K, Aprelikova O, Armstrong E, Morris S, Alitalo K: Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts. Oncogene. 1993 Nov;8(11):2931-7. 7692369
  10. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. 15340161
  11. Borg JP, deLapeyriere O, Noguchi T, Rottapel R, Dubreuil P, Birnbaum D: Biochemical characterization of two isoforms of FLT4, a VEGF receptor-related tyrosine kinase. Oncogene. 1995 Mar 2;10(5):973-84. 7898938
  12. Fournier E, Dubreuil P, Birnbaum D, Borg JP: Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor. Oncogene. 1995 Sep 7;11(5):921-31. 7675451
  13. Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA: 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. 1998 Jan 20;95(2):548-53. 9435229
  14. Makinen T, Veikkola T, Mustjoki S, Karpanen T, Catimel B, Nice EC, Wise L, Mercer A, Kowalski H, Kerjaschki D, Stacker SA, Achen MG, Alitalo K: Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J. 2001 Sep 3;20(17):4762-73. 11532940
  15. Dixelius J, Makinen T, Wirzenius M, Karkkainen MJ, Wernstedt C, Alitalo K, Claesson-Welsh L: Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites. J Biol Chem. 2003 Oct 17;278(42):40973-9. Epub 2003 Jul 24. 12881528
  16. Alam A, Herault JP, Barron P, Favier B, Fons P, Delesque-Touchard N, Senegas I, Laboudie P, Bonnin J, Cassan C, Savi P, Ruggeri B, Carmeliet P, Bono F, Herbert JM: Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity. Biochem Biophys Res Commun. 2004 Nov 12;324(2):909-15. 15474514
  17. Wang JF, Zhang X, Groopman JE: Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress. J Biol Chem. 2004 Jun 25;279(26):27088-97. Epub 2004 Apr 21. 15102829
  18. Salameh A, Galvagni F, Bardelli M, Bussolino F, Oliviero S: Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation, migration, and survival of endothelial cells through the activation of ERK, AKT, and JNK pathways. Blood. 2005 Nov 15;106(10):3423-31. Epub 2005 Aug 2. 16076871
  19. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. 16335952
  20. Garces CA, Kurenova EV, Golubovskaya VM, Cance WG: Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells. Cancer Res. 2006 Feb 1;66(3):1446-54. 16452200
  21. Goldman J, Rutkowski JM, Shields JD, Pasquier MC, Cui Y, Schmokel HG, Willey S, Hicklin DJ, Pytowski B, Swartz MA: Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesis. FASEB J. 2007 Apr;21(4):1003-12. Epub 2007 Jan 8. 17210781
  22. Matsuura M, Onimaru M, Yonemitsu Y, Suzuki H, Nakano T, Ishibashi H, Shirasuna K, Sueishi K: Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells. Am J Pathol. 2009 Oct;175(4):1709-21. doi: 10.2353/ajpath.2009.081139. Epub 2009 Sep 24. 19779139
  23. Kurenova EV, Hunt DL, He D, Magis AT, Ostrov DA, Cance WG: Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo. J Med Chem. 2009 Aug 13;52(15):4716-24. doi: 10.1021/jm900159g. 19610651
  24. Au AC, Hernandez PA, Lieber E, Nadroo AM, Shen YM, Kelley KA, Gelb BD, Diaz GA: Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans. Am J Hum Genet. 2010 Sep 10;87(3):436-44. doi: 10.1016/j.ajhg.2010.08.008. 20826270
  25. Galvagni F, Pennacchini S, Salameh A, Rocchigiani M, Neri F, Orlandini M, Petraglia F, Gotta S, Sardone GL, Matteucci G, Terstappen GC, Oliviero S: Endothelial cell adhesion to the extracellular matrix induces c-Src-dependent VEGFR-3 phosphorylation without the activation of the receptor intrinsic kinase activity. Circ Res. 2010 Jun 25;106(12):1839-48. doi: 10.1161/CIRCRESAHA.109.206326. Epub 2010 Apr 29. 20431062
  26. Nilsson I, Bahram F, Li X, Gualandi L, Koch S, Jarvius M, Soderberg O, Anisimov A, Kholova I, Pytowski B, Baldwin M, Yla-Herttuala S, Alitalo K, Kreuger J, Claesson-Welsh L: VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts. EMBO J. 2010 Apr 21;29(8):1377-88. doi: 10.1038/emboj.2010.30. Epub 2010 Mar 11. 20224550
  27. Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Luthi U, Barberis A, Benjamin LE, Makinen T, Nobes CD, Adams RH: Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 2010 May 27;465(7297):483-6. doi: 10.1038/nature09002. 20445537
  28. Yuen D, Pytowski B, Chen L: Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stages. Invest Ophthalmol Vis Sci. 2011 Apr 20;52(5):2593-7. doi: 10.1167/iovs.10-6408. 21273538
  29. Roskoski R Jr: VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem Biophys Res Commun. 2008 Oct 24;375(3):287-91. doi: 10.1016/j.bbrc.2008.07.121. Epub 2008 Aug 3. 18680722
  30. Lohela M, Bry M, Tammela T, Alitalo K: VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. Curr Opin Cell Biol. 2009 Apr;21(2):154-65. doi: 10.1016/j.ceb.2008.12.012. Epub 2009 Feb 21. 19230644
  31. Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L: Signal transduction by vascular endothelial growth factor receptors. Biochem J. 2011 Jul 15;437(2):169-83. doi: 10.1042/BJ20110301. 21711246
  32. Al-Rawi MA, Jiang WG: Lymphangiogenesis and cancer metastasis. Front Biosci (Landmark Ed). 2011 Jan 1;16:723-39. 21196198
  33. Ferrell RE, Levinson KL, Esman JH, Kimak MA, Lawrence EC, Barmada MM, Finegold DN: Hereditary lymphedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet. 1998 Dec;7(13):2073-8. 9817924
  34. Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M: Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet. 2000 Aug;67(2):295-301. Epub 2000 Jun 9. 10856194
  35. Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA, Alitalo K, Finegold DN: Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. 2000 Jun;25(2):153-9. 10835628
  36. Walter JW, North PE, Waner M, Mizeracki A, Blei F, Walker JW, Reinisch JF, Marchuk DA: Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma. Genes Chromosomes Cancer. 2002 Mar;33(3):295-303. 11807987
  37. Ghalamkarpour A, Morlot S, Raas-Rothschild A, Utkus A, Mulliken JB, Boon LM, Vikkula M: Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. Clin Genet. 2006 Oct;70(4):330-5. 16965327
  38. Spiegel R, Ghalamkarpour A, Daniel-Spiegel E, Vikkula M, Shalev SA: Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3. J Hum Genet. 2006;51(10):846-50. Epub 2006 Aug 19. 16924388
  39. Butler MG, Dagenais SL, Rockson SG, Glover TW: A novel VEGFR3 mutation causes Milroy disease. Am J Med Genet A. 2007 Jun 1;143A(11):1212-7. 17458866
  40. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846
  41. Ghalamkarpour A, Holnthoner W, Saharinen P, Boon LM, Mulliken JB, Alitalo K, Vikkula M: Recessive primary congenital lymphoedema caused by a VEGFR3 mutation. J Med Genet. 2009 Jun;46(6):399-404. doi: 10.1136/jmg.2008.064469. Epub 2009 Mar 15. 19289394
  42. Melikhan-Revzin S, Kurolap A, Dagan E, Mory A, Gershoni-Baruch R: A Novel Missense Mutation in FLT4 Causes Autosomal Recessive Hereditary Lymphedema. Lymphat Res Biol. 2015 Jun;13(2):107-11. doi: 10.1089/lrb.2014.0044. Epub 2015 Jun 2. 26091405