NameAngiopoietin-1 receptor
Synonyms
  • 2.7.10.1
  • Endothelial tyrosine kinase
  • hTIE2
  • p140 TEK
  • TIE2
  • Tunica interna endothelial cell kinase
  • Tyrosine kinase with Ig and EGF homology domains-2
  • Tyrosine-protein kinase receptor TEK
  • Tyrosine-protein kinase receptor TIE-2
  • VMCM
  • VMCM1
Gene NameTEK
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037228|Angiopoietin-1 receptor
MDSLASLVLCGVSLLLSGTVEGAMDLILINSLPLVSDAETSLTCIASGWRPHEPITIGRD
FEALMNQHQDPLEVTQDVTREWAKKVVWKREKASKINGAYFCEGRVRGEAIRIRTMKMRQ
QASFLPATLTMTVDKGDNVNISFKKVLIKEEDAVIYKNGSFIHSVPRHEVPDILEVHLPH
AQPQDAGVYSARYIGGNLFTSAFTRLIVRRCEAQKWGPECNHLCTACMNNGVCHEDTGEC
ICPPGFMGRTCEKACELHTFGRTCKERCSGQEGCKSYVFCLPDPYGCSCATGWKGLQCNE
ACHPGFYGPDCKLRCSCNNGEMCDRFQGCLCSPGWQGLQCEREGIQRMTPKIVDLPDHIE
VNSGKFNPICKASGWPLPTNEEMTLVKPDGTVLHPKDFNHTDHFSVAIFTIHRILPPDSG
VWVCSVNTVAGMVEKPFNISVKVLPKPLNAPNVIDTGHNFAVINISSEPYFGDGPIKSKK
LLYKPVNHYEAWQHIQVTNEIVTLNYLEPRTEYELCVQLVRRGEGGEGHPGPVRRFTTAS
IGLPPPRGLNLLPKSQTTLNLTWQPIFPSSEDDFYVEVERRSVQKSDQQNIKVPGNLTSV
LLNNLHPREQYVVRARVNTKAQGEWSEDLTAWTLSDILPPQPENIKISNITHSSAVISWT
ILDGYSISSITIRYKVQGKNEDQHVDVKIKNATITQYQLKGLEPETAYQVDIFAENNIGS
SNPAFSHELVTLPESQAPADLGGGKMLLIAILGSAGMTCLTVLLAFLIILQLKRANVQRR
MAQAFQNVREEPAVQFNSGTLALNRKVKNNPDPTIYPVLDWNDIKFQDVIGEGNFGQVLK
ARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRGYLYL
AIEYAPHGNLLDFLRKSRVLETDPAFAIANSTASTLSSQQLLHFAADVARGMDYLSQKQF
IHRDLAARNILVGENYVAKIADFGLSRGQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSD
VWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPY
ERPSFAQILVSLNRMLEERKTYVNTTLYEKFTYAGIDCSAEEAA
Number of residues1124
Molecular Weight125829.005
Theoretical pI6.88
GO Classification
Functions
  • transmembrane receptor protein tyrosine kinase activity
  • protein tyrosine kinase activity
  • receptor activity
  • ATP binding
  • protein kinase activity
Processes
  • negative regulation of angiogenesis
  • positive regulation of protein phosphorylation
  • vascular endothelial growth factor receptor signaling pathway
  • endothelial cell proliferation
  • positive regulation of endothelial cell proliferation
  • transmembrane receptor protein tyrosine kinase signaling pathway
  • positive regulation of protein import into nucleus
  • Fc-epsilon receptor signaling pathway
  • sprouting angiogenesis
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • positive regulation of actin cytoskeleton reorganization
  • endochondral ossification
  • blood coagulation
  • response to estrogen
  • definitive hemopoiesis
  • leukocyte migration
  • negative regulation of inflammatory response
  • positive regulation of intracellular signal transduction
  • response to cAMP
  • positive regulation of focal adhesion assembly
  • activation of MAPKK activity
  • cell-matrix adhesion
  • small GTPase mediated signal transduction
  • regulation of NIK/NF-kappaB signaling
  • fibroblast growth factor receptor signaling pathway
  • cell-cell signaling
  • angiogenesis
  • Tie signaling pathway
  • heart development
  • positive regulation of protein kinase B signaling
  • positive regulation of endothelial cell migration
  • glomerulus vasculature development
  • insulin receptor signaling pathway
  • heart trabecula formation
  • positive regulation of cytokine secretion involved in immune response
  • MAPK cascade
  • organ regeneration
  • positive regulation of ERK1 and ERK2 cascade
  • regulation of endothelial cell apoptotic process
  • negative regulation of apoptotic process
  • protein oligomerization
  • axon guidance
  • positive regulation of phosphatidylinositol 3-kinase activity
  • regulation of establishment or maintenance of cell polarity
  • neurotrophin TRK receptor signaling pathway
  • substrate adhesion-dependent cell spreading
  • epidermal growth factor receptor signaling pathway
  • protein autophosphorylation
  • signal transduction
  • positive regulation of peptidyl-serine phosphorylation
  • single organismal cell-cell adhesion
  • innate immune response
  • negative regulation of endothelial cell apoptotic process
  • Ras protein signal transduction
  • regulation of vascular permeability
  • peptidyl-tyrosine phosphorylation
  • positive regulation of angiogenesis
  • response to hypoxia
Components
  • cell-cell junction
  • integral component of plasma membrane
  • basolateral plasma membrane
  • cytoskeleton
  • membrane raft
  • extracellular region
  • plasma membrane
  • apical plasma membrane
  • basal plasma membrane
  • cell surface
  • perinuclear region of cytoplasm
  • focal adhesion
  • microvillus
General FunctionTransmembrane receptor protein tyrosine kinase activity
Specific FunctionTyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1.
Pfam Domain Function
Transmembrane Regions749-769
GenBank Protein IDNot Available
UniProtKB IDQ02763
UniProtKB Entry NameTIE2_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0017082|Angiopoietin-1 receptor (TEK)
ATGGACTCTTTAGCCAGCTTAGTTCTCTGTGGAGTCAGCTTGCTCCTTTCTGGAACTGTG
GAAGGTGCCATGGACTTGATCTTGATCAATTCCCTACCTCTTGTATCTGATGCTGAAACA
TCTCTCACCTGCATTGCCTCTGGGTGGCGCCCCCATGAGCCCATCACCATAGGAAGGGAC
TTTGAAGCCTTAATGAACCAGCACCAGGATCCGCTGGAAGTTACTCAAGATGTGACCAGA
GAATGGGCTAAAAAAGTTGTTTGGAAGAGAGAAAAGGCTAGTAAGATCAATGGTGCTTAT
TTCTGTGAAGGGCGAGTTCGAGGAGAGGCAATCAGGATACGAACCATGAAGATGCGTCAA
CAAGCTTCCTTCCTACCAGCTACTTTAACTATGACTGTGGACAAGGGAGATAACGTGAAC
ATATCTTTCAAAAAGGTATTGATTAAAGAAGAAGATGCAGTGATTTACAAAAATGGTTCC
TTCATCCATTCAGTGCCCCGGCATGAAGTACCTGATATTCTAGAAGTACACCTGCCTCAT
GCTCAGCCCCAGGATGCTGGAGTGTACTCGGCCAGGTATATAGGAGGAAACCTCTTCACC
TCGGCCTTCACCAGGCTGATAGTCCGGAGATGTGAAGCCCAGAAGTGGGGACCTGAATGC
AACCATCTCTGTACTGCTTGTATGAACAATGGTGTCTGCCATGAAGATACTGGAGAATGC
ATTTGCCCTCCTGGGTTTATGGGAAGGACGTGTGAGAAGGCTTGTGAACTGCACACGTTT
GGCAGAACTTGTAAAGAAAGGTGCAGTGGACAAGAGGGATGCAAGTCTTATGTGTTCTGT
CTCCCTGACCCCTATGGGTGTTCCTGTGCCACAGGCTGGAAGGGTCTGCAGTGCAATGAA
GCATGCCACCCTGGTTTTTACGGGCCAGATTGTAAGCTTAGGTGCAGCTGCAACAATGGG
GAGATGTGTGATCGCTTCCAAGGATGTCTCTGCTCTCCAGGATGGCAGGGGCTCCAGTGT
GAGAGAGAAGGCATACCGAGGATGACCCCAAAGATAGTGGATTTGCCAGATCATATAGAA
GTAAACAGTGGTAAATTTAATCCCATTTGCAAAGCTTCTGGCTGGCCGCTACCTACTAAT
GAAGAAATGACCCTGGTGAAGCCGGATGGGACAGTGCTCCATCCAAAAGACTTTAACCAT
ACGGATCATTTCTCAGTAGCCATATTCACCATCCACCGGATCCTCCCCCCTGACTCAGGA
GTTTGGGTCTGCAGTGTGAACACAGTGGCTGGGATGGTGGAAAAGCCCTTCAACATTTCT
GTTAAAGTTCTTCCAAAGCCCCTGAATGCCCCAAACGTGATTGACACTGGACATAACTTT
GCTGTCATCAACATCAGCTCTGAGCCTTACTTTGGGGATGGACCAATCAAATCCAAGAAG
CTTCTATACAAACCCGTTAATCACTATGAGGCTTGGCAACATATTCAAGTGACAAATGAG
ATTGTTACACTCAACTATTTGGAACCTCGGACAGAATATGAACTCTGTGTGCAACTGGTC
CGTCGTGGAGAGGGTGGGGAAGGGCATCCTGGACCTGTGAGACGCTTCACAACAGCTTCT
ATCGGACTCCCTCCTCCAAGAGGTCTAAATCTCCTGCCTAAAAGTCAGACCACTCTAAAT
TTGACCTGGCAACCAATATTTCCAAGCTCGGAAGATGACTTTTATGTTGAAGTGGAGAGA
AGGTCTGTGCAAAAAAGTGATCAGCAGAATATTAAAGTTCCAGGCAACTTGACTTCGGTG
CTACTTAACAACTTACATCCCAGGGAGCAGTACGTGGTCCGAGCTAGAGTCAACACCAAG
GCCCAGGGGGAATGGAGTGAAGATCTCACTGCTTGGACCCTTAGTGACATTCTTCCTCCT
CAACCAGAAAACATCAAGATTTCCAACATTACACACTCCTCAGCTGTGATTTCTTGGACA
ATATTGGATGGCTATTCTATTTCTTCTATTACTATCCGTTACAAGGTTCAAGGCAAGAAT
GAAGACCAGCACGTTGATGTGAAGATAAAGAATGCCACCATCACTCAGTATCAGCTCAAG
GGCCTAGAGCCTGAAACAGCATACCAGGTGGACATTTTTGCAGAGAACAACATAGGGTCA
AGCAACCCAGCCTTTTCTCATGAACTGGTGACCCTCCCAGAATCTCAAGCACCAGCGGAC
CTCGGAGGGGGGAAGATGCTGCTTATAGCCATCCTTGGCTCTGCTGGAATGACCTGCCTG
ACTGTGCTGTTGGCCTTTCTGATCATATTGCAATTGAAGAGGGCAAATGTGCAAAGGAGA
ATGGCCCAAGCCTTCCAAAACGTGAGGGAAGAACCAGCTGTGCAGTTCAACTCAGGGACT
CTGGCCCTAAACAGGAAGGTCAAAAACAACCCAGATCCTACAATTTATCCAGTGCTTGAC
TGGAATGACATCAAATTTCAAGATGTGATTGGGGAGGGCAATTTTGGCCAAGTTCTTAAG
GCGCGCATCAAGAAGGATGGGTTACGGATGGATGCTGCCATCAAAAGAATGAAAGAATAT
GCCTCCAAAGATGATCACAGGGACTTTGCAGGAGAACTGGAAGTTCTTTGTAAACTTGGA
CACCATCCAAACATCATCAATCTCTTAGGAGCATGTGAACATCGAGGCTACTTGTACCTG
GCCATTGAGTACGCGCCCCATGGAAACCTTCTGGACTTCCTTCGCAAGAGCCGTGTGCTG
GAGACGGACCCAGCATTTGCCATTGCCAATAGCACCGCGTCCACACTGTCCTCCCAGCAG
CTCCTTCACTTCGCTGCCGACGTGGCCCGGGGCATGGACTACTTGAGCCAAAAACAGTTT
ATCCACAGGGATCTGGCTGCCAGAAACATTTTAGTTGGTGAAAACTATGTGGCAAAAATA
GCAGATTTTGGATTGTCCCGAGGTCAAGAGGTGTATGTGAAAAAGACAATGGGAAGGCTC
CCAGTGCGCTGGATGGCCATCGAGTCACTGAATTACAGTGTGTACACAACCAACAGTGAT
GTATGGTCCTATGGTGTGTTACTATGGGAGATTGTTAGCTTAGGAGGCACACCCTACTGC
GGGATGACTTGTGCAGAACTCTACGAGAAGCTGCCCCAGGGCTACAGACTGGAGAAGCCC
CTGAACTGTGATGATGAGGTGTATGATCTAATGAGACAATGCTGGCGGGAGAAGCCTTAT
GAGAGGCCATCATTTGCCCAGATATTGGTGTCCTTAAACAGAATGTTAGAGGAGCGAAAG
ACCTACGTGAATACCACGCTTTATGAGAAGTTTACTTATGCAGGAATTGACTGTTCTGCT
GAAGAAGCGGCCTAG
GenBank Gene IDL06139
GeneCard IDNot Available
GenAtlas IDTEK
HGNC IDHGNC:11724
Chromosome Location9
Locus9p21
References
  1. Ziegler SF, Bird TA, Schneringer JA, Schooley KA, Baum PR: Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta. Oncogene. 1993 Mar;8(3):663-70. 8382358
  2. 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
  3. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. 15164053
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. 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
  6. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997 Jul 4;277(5322):55-60. 9204896
  7. Reusch P, Barleon B, Weindel K, Martiny-Baron G, Godde A, Siemeister G, Marme D: Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood. Angiogenesis. 2001;4(2):123-31. 11806244
  8. Murray BW, Padrique ES, Pinko C, McTigue MA: Mechanistic effects of autophosphorylation on receptor tyrosine kinase catalysis: enzymatic characterization of Tie2 and phospho-Tie2. Biochemistry. 2001 Aug 28;40(34):10243-53. 11513602
  9. Cascone I, Audero E, Giraudo E, Napione L, Maniero F, Philips MR, Collard JG, Serini G, Bussolino F: Tie-2-dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1. Blood. 2003 Oct 1;102(7):2482-90. Epub 2003 Jun 19. 12816861
  10. Hughes DP, Marron MB, Brindle NP: The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a novel nuclear factor-kappaB inhibitor ABIN-2. Circ Res. 2003 Apr 4;92(6):630-6. Epub 2003 Feb 27. 12609966
  11. Lee HJ, Cho CH, Hwang SJ, Choi HH, Kim KT, Ahn SY, Kim JH, Oh JL, Lee GM, Koh GY: Biological characterization of angiopoietin-3 and angiopoietin-4. FASEB J. 2004 Aug;18(11):1200-8. 15284220
  12. Audero E, Cascone I, Maniero F, Napione L, Arese M, Lanfrancone L, Bussolino F: Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells. J Biol Chem. 2004 Mar 26;279(13):13224-33. Epub 2003 Dec 9. 14665640
  13. Saharinen P, Kerkela K, Ekman N, Marron M, Brindle N, Lee GM, Augustin H, Koh GY, Alitalo K: Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. J Cell Biol. 2005 Apr 25;169(2):239-43. 15851516
  14. Fukuhara S, Sako K, Minami T, Noda K, Kim HZ, Kodama T, Shibuya M, Takakura N, Koh GY, Mochizuki N: Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. Nat Cell Biol. 2008 May;10(5):513-26. doi: 10.1038/ncb1714. Epub 2008 Apr 20. 18425120
  15. Saharinen P, Eklund L, Miettinen J, Wirkkala R, Anisimov A, Winderlich M, Nottebaum A, Vestweber D, Deutsch U, Koh GY, Olsen BR, Alitalo K: Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol. 2008 May;10(5):527-37. doi: 10.1038/ncb1715. Epub 2008 Apr 20. 18425119
  16. Yacyshyn OK, Lai PF, Forse K, Teichert-Kuliszewska K, Jurasz P, Stewart DJ: Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. Angiogenesis. 2009;12(1):25-33. doi: 10.1007/s10456-008-9126-0. Epub 2009 Jan 1. 19116766
  17. Wehrle C, Van Slyke P, Dumont DJ: Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for internalization and degradation. Biochem J. 2009 Oct 12;423(3):375-80. doi: 10.1042/BJ20091010. 19689429
  18. Winderlich M, Keller L, Cagna G, Broermann A, Kamenyeva O, Kiefer F, Deutsch U, Nottebaum AF, Vestweber D: VE-PTP controls blood vessel development by balancing Tie-2 activity. J Cell Biol. 2009 May 18;185(4):657-71. doi: 10.1083/jcb.200811159. 19451274
  19. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. 19159218
  20. Yuan HT, Khankin EV, Karumanchi SA, Parikh SM: Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol. 2009 Apr;29(8):2011-22. doi: 10.1128/MCB.01472-08. Epub 2009 Feb 17. 19223473
  21. Martin V, Liu D, Fueyo J, Gomez-Manzano C: Tie2: a journey from normal angiogenesis to cancer and beyond. Histol Histopathol. 2008 Jun;23(6):773-80. 18366015
  22. Fukuhara S, Sako K, Noda K, Nagao K, Miura K, Mochizuki N: Tie2 is tied at the cell-cell contacts and to extracellular matrix by angiopoietin-1. Exp Mol Med. 2009 Mar 31;41(3):133-9. doi: 10.3858/emm.2009.41.3.016. 19293632
  23. Augustin HG, Koh GY, Thurston G, Alitalo K: Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol. 2009 Mar;10(3):165-77. doi: 10.1038/nrm2639. 19234476
  24. Fukuhara S, Sako K, Noda K, Zhang J, Minami M, Mochizuki N: Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis. Histol Histopathol. 2010 Mar;25(3):387-96. 20054809
  25. Huang H, Bhat A, Woodnutt G, Lappe R: Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer. 2010 Aug;10(8):575-85. doi: 10.1038/nrc2894. 20651738
  26. Shewchuk LM, Hassell AM, Ellis B, Holmes WD, Davis R, Horne EL, Kadwell SH, McKee DD, Moore JT: Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail. Structure. 2000 Nov 15;8(11):1105-13. 11080633
  27. Barton WA, Tzvetkova-Robev D, Miranda EP, Kolev MV, Rajashankar KR, Himanen JP, Nikolov DB: Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex. Nat Struct Mol Biol. 2006 Jun;13(6):524-32. Epub 2006 May 28. 16732286
  28. Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Caenepeel S, Cee VJ, Chaffee SC, Emery M, Fretland J, Gallant P, Gu Y, Johnson RE, Kim JL, Long AM, Morrison M, Olivieri PR, Patel VF, Polverino A, Rose P, Wang L, Zhao H: Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2886-9. Epub 2007 Feb 25. 17350837
  29. Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Bready J, Caenepeel S, Cee VJ, Chaffee SC, Coxon A, Emery M, Fretland J, Gallant P, Gu Y, Hoffman D, Johnson RE, Kendall R, Kim JL, Long AM, Morrison M, Olivieri PR, Patel VF, Polverino A, Rose P, Tempest P, Wang L, Whittington DA, Zhao H: Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor. J Med Chem. 2007 Feb 22;50(4):611-26. Epub 2007 Jan 25. 17253678
  30. Luke RW, Ballard P, Buttar D, Campbell L, Curwen J, Emery SC, Griffen AM, Hassall L, Hayter BR, Jones CD, McCoull W, Mellor M, Swain ML, Tucker JA: Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6670-4. doi: 10.1016/j.bmcl.2009.10.001. Epub 2009 Oct 13. 19854647
  31. Vikkula M, Boon LM, Carraway KL 3rd, Calvert JT, Diamonti AJ, Goumnerov B, Pasyk KA, Marchuk DA, Warman ML, Cantley LC, Mulliken JB, Olsen BR: Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell. 1996 Dec 27;87(7):1181-90. 8980225
  32. Calvert JT, Riney TJ, Kontos CD, Cha EH, Prieto VG, Shea CR, Berg JN, Nevin NC, Simpson SA, Pasyk KA, Speer MC, Peters KG, Marchuk DA: Allelic and locus heterogeneity in inherited venous malformations. Hum Mol Genet. 1999 Jul;8(7):1279-89. 10369874
  33. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. 16959974
  34. 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
  35. Wouters V, Limaye N, Uebelhoer M, Irrthum A, Boon LM, Mulliken JB, Enjolras O, Baselga E, Berg J, Dompmartin A, Ivarsson SA, Kangesu L, Lacassie Y, Murphy J, Teebi AS, Penington A, Rieu P, Vikkula M: Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects. Eur J Hum Genet. 2010 Apr;18(4):414-20. doi: 10.1038/ejhg.2009.193. Epub 2009 Nov 4. 19888299