Hepatocyte growth factor receptor

NameHepatocyte growth factor receptor
Synonyms
  • 2.7.10.1
  • HGF receptor
  • HGF/SF receptor
  • Proto-oncogene c-Met
  • Scatter factor receptor
  • SF receptor
  • Tyrosine-protein kinase Met
Gene NameMET
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037101|Hepatocyte growth factor receptor
MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEH
HIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMAL
VVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPE
FRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECIL
TEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS
AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEF
TTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFL
LDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW
CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKK
TRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVIT
SISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF
AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVH
EAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPV
FKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL
LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQ
IKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGS
CRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHF
NEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVL
SLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKF
VHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKF
TTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCW
HPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVD
TRPASFWETS
Number of residues1390
Molecular Weight155540.035
Theoretical pI7.34
GO Classification
Functions
  • protein tyrosine kinase activity
  • protein phosphatase binding
  • hepatocyte growth factor-activated receptor activity
  • ATP binding
Processes
  • negative regulation of autophagy
  • negative regulation of hydrogen peroxide-mediated programmed cell death
  • positive chemotaxis
  • cell proliferation
  • positive regulation of endothelial cell chemotaxis
  • semaphorin-plexin signaling pathway
  • axon guidance
  • peptidyl-tyrosine phosphorylation
  • positive regulation of transcription from RNA polymerase II promoter
  • cell surface receptor signaling pathway
  • branching morphogenesis of an epithelial tube
  • signal transduction
  • endothelial cell morphogenesis
  • hepatocyte growth factor receptor signaling pathway
Components
  • plasma membrane
  • cell surface
  • integral component of membrane
  • integral component of plasma membrane
  • basal plasma membrane
  • extracellular region
General FunctionProtein tyrosine kinase activity
Specific FunctionReceptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.
Pfam Domain Function
Transmembrane Regions933-955
GenBank Protein ID307196
UniProtKB IDP08581
UniProtKB Entry NameMET_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0010644|Hepatocyte growth factor receptor (MET)
ATGAAGGCCCCCGCTGTGCTTGCACCTGGCATCCTCGTGCTCCTGTTTACCTTGGTGCAG
AGGAGCAATGGGGAGTGTAAAGAGGCACTAGCAAAGTCCGAGATGAATGTGAATATGAAG
TATCAGCTTCCCAACTTCACCGCGGAAACACCCATCCAGAATGTCATTCTACATGAGCAT
CACATTTTCCTTGGTGCCACTAACTACATTTATGTTTTAAATGAGGAAGACCTTCAGAAG
GTTGCTGAGTACAAGACTGGGCCTGTGCTGGAACACCCAGATTGTTTCCCATGTCAGGAC
TGCAGCAGCAAAGCCAATTTATCAGGAGGTGTTTGGAAAGATAACATCAACATGGCTCTA
GTTGTCGACACCTACTATGATGATCAACTCATTAGCTGTGGCAGCGTCAACAGAGGGACC
TGCCAGCGACATGTCTTTCCCCACAATCATACTGCTGACATACAGTCGGAGGTTCACTGC
ATATTCTCCCCACAGATAGAAGAGCCCAGCCAGTGTCCTGACTGTGTGGTGAGCGCCCTG
GGAGCCAAAGTCCTTTCATCTGTAAAGGACCGGTTCATCAACTTCTTTGTAGGCAATACC
ATAAATTCTTCTTATTTCCCAGATCATCCATTGCATTCGATATCAGTGAGAAGGCTAAAG
GAAACGAAAGATGGTTTTATGTTTTTGACGGACCAGTCCTACATTGATGTTTTACCTGAG
TTCAGAGATTCTTACCCCATTAAGTATGTCCATGCCTTTGAAAGCAACAATTTTATTTAC
TTCTTGACGGTCCAAAGGGAAACTCTAGATGCTCAGACTTTTCACACAAGAATAATCAGG
TTCTGTTCCATAAACTCTGGATTGCATTCCTACATGGAAATGCCTCTGGAGTGTATTCTC
ACAGAAAAGAGAAAAAAGAGATCCACAAAGAAGGAAGTGTTTAATATACTTCAGGCTGCG
TATGTCAGCAAGCCTGGGGCCCAGCTTGCTAGACAAATAGGAGCCAGCCTGAATGATGAC
ATTCTTTTCGGGGTGTTCGCACAAAGCAAGCCAGATTCTGCCGAACCAATGGATCGATCT
GCCATGTGTGCATTCCCTATCAAATATGTCAACGACTTCTTCAACAAGATCGTCAACAAA
AACAATGTGAGATGTCTCCAGCATTTTTACGGACCCAATCATGAGCACTGCTTTAATAGG
ACACTTCTGAGAAATTCATCAGGCTGTGAAGCGCGCCGTGATGAATATCGAACAGAGTTT
ACCACAGCTTTGCAGCGCGTTGACTTATTCATGGGTCAATTCAGCGAAGTCCTCTTAACA
TCTATATCCACCTTCATTAAAGGAGACCTCACCATAGCTAATCTTGGGACATCAGAGGGT
CGCTTCATGCAGGTTGTGGTTTCTCGATCAGGACCATCAACCCCTCATGTGAATTTTCTC
CTGGACTCCCATCCAGTGTCTCCAGAAGTGATTGTGGAGCATACATTAAACCAAAATGGC
TACACACTGGTTATCACTGGGAAGAAGATCACGAAGATCCCATTGAATGGCTTGGGCTGC
AGACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCACCCTTTGTTCAGTGTGGCTGG
TGCCACGACAAATGTGTGCGATCGGAGGAATGCCTGAGCGGGACATGGACTCAACAGATC
TGTCTGCCTGCAATCTACAAGGTTTTCCCAAATAGTGCACCCCTTGAAGGAGGGACAAGG
CTGACCATATGTGGCTGGGACTTTGGATTTCGGAGGAATAATAAATTTGATTTAAAGAAA
ACTAGAGTTCTCCTTGGAAATGAGAGCTGCACCTTGACTTTAAGTGAGAGCACGATGAAT
ACATTGAAATGCACAGTTGGTCCTGCCATGAATAAGCATTTCAATATGTCCATAATTATT
TCAAATGGCCACGGGACAACACAATACAGTACATTCTCCTATGTGGATCCTGTAATAACA
AGTATTTCGCCGAAATACGGTCCTATGGCTGGTGGCACTTTACTTACTTTAACTGGAAAT
TACCTAAACAGTGGGAATTCTAGACACATTTCAATTGGTGGAAAAACATGTACTTTAAAA
AGTGTGTCAAACAGTATTCTTGAATGTTATACCCCAGCCCAAACCATTTCAACTGAGTTT
GCTGTTAAATTGAAAATTGACTTAGCCAACCGAGAGACAAGCATCTTCAGTTACCGTGAA
GATCCCATTGTCTATGAAATTCATCCAACCAAATCTTTTATTAGTGGTGGGAGCACAATA
ACAGGTGTTGGGAAAAACCTGAATTCAGTTAGTGTCCCGAGAATGGTCATAAATGTGCAT
GAAGCAGGAAGGAACTTTACAGTGGCATGTCAACATCGCTCTAATTCAGAGATAATCTGT
TGTACCACTCCTTCCCTGCAACAGCTGAATCTGCAACTCCCCCTGAAAACCAAAGCCTTT
TTCATGTTAGATGGGATCCTTTCCAAATACTTTGATCTCATTTATGTACATAATCCTGTG
TTTAAGCCTTTTGAAAAGCCAGTGATGATCTCAATGGGCAATGAAAATGTACTGGAAATT
AAGGGAAATGATATTGACCCTGAAGCAGTTAAAGGTGAAGTGTTAAAAGTTGGAAATAAG
AGCTGTGAGAATATACACTTACATTCTGAAGCCGTTTTATGCACGGTCCCCAATGACCTG
CTGAAATTGAACAGCGAGCTAAATATAGAGTGGAAGCAAGCAATTTCTTCAACCGTCCTT
GGAAAAGTAATAGTTCAACCAGATCAGAATTTCACAGGATTGATTGCTGGTGTTGTCTCA
ATATCAACAGCACTGTTATTACTACTTGGGTTTTTCCTGTGGCTGAAAAAGAGAAAGCAA
ATTAAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTCCTCATTTG
GATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAAATGAATCT
GTAGACTACCGAGCTACTTTTCCAGAAGATCAGTTTCCTAATTCATCTCAGAACGGTTCA
TGCCGACAAGTGCAGTATCCTCTGACAGACATGTCCCCCATCCTAACTAGTGGGGACTCT
GATATATCCAGTCCATTACTGCAAAATACTGTCCACATTGACCTCAGTGCTCTAAATCCA
GAGCTGGTCCAGGCAGTGCAGCATGTAGTGATTGGGCCCAGTAGCCTGATTGTGCATTTC
AATGAAGTCATAGGAAGAGGGCATTTTGGTTGTGTATATCATGGGACTTTGTTGGACAAT
GATGGCAAGAAAATTCACTGTGCTGTGAAATCCTTGAACAGAATCACTGACATAGGAGAA
GTTTCCCAATTTCTGACCGAGGGAATCATCATGAAAGATTTTAGTCATCCCAATGTCCTC
TCGCTCCTGGGAATCTGCCTGCGAAGTGAAGGGTCTCCGCTGGTGGTCCTACCATACATG
AAACATGGAGATCTTCGAAATTTCATTCGAAATGAGACTCATAATCCAACTGTAAAAGAT
CTTATTGGCTTTGGTCTTCAAGTAGCCAAAGGCATGAAATATCTTGCAAGCAAAAAGTTT
GTCCACAGAGACTTGGCTGCAAGAAACTGTATGCTGGATGAAAAATTCACAGTCAAGGTT
GCTGATTTTGGTCTTGCCAGAGACATGTATGATAAAGAATACTATAGTGTACACAACAAA
ACAGGTGCAAAGCTGCCAGTGAAGTGGATGGCTTTGGAAAGTCTGCAAACTCAAAAGTTT
ACCACCAAGTCAGATGTGTGGTCCTTTGGCGTGCTCCTCTGGGAGCTGATGACAAGAGGA
GCCCCACCTTATCCTGACGTAAACACCTTTGATATAACTGTTTACTTGTTGCAAGGGAGA
AGACTCCTACAACCCGAATACTGCCCAGACCCCTTATATGAAGTAATGCTAAAATGCTGG
CACCCTAAAGCCGAAATGCGCCCATCCTTTTCTGAACTGGTGTCCCGGATATCAGCGATC
TTCTCTACTTTCATTGGGGAGCACTATGTCCATGTGAACGCTACTTATGTGAACGTAAAA
TGTGTCGCTCCGTATCCTTCTCTGTTGTCATCAGAAGATAACGCTGATGATGAGGTGGAC
ACACGACCAGCCTCCTTCTGGGAGACATCATAG
GenBank Gene IDJ02958
GeneCard IDNot Available
GenAtlas IDMET
HGNC IDHGNC:7029
Chromosome Location7
Locus7q31
References
  1. Park M, Dean M, Kaul K, Braun MJ, Gonda MA, Vande Woude G: Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379-83. 2819873
  2. 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
  3. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. 12853948
  4. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. 12690205
  5. 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
  6. Chan AM, King HW, Tempest PR, Deakin EA, Cooper CS, Brookes P: Primary structure of the met protein tyrosine kinase domain. Oncogene. 1987 May;1(2):229-33. 3325883
  7. Lee ST, Strunk KM, Spritz RA: A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. Oncogene. 1993 Dec;8(12):3403-10. 8247543
  8. Dean M, Park M, Le Beau MM, Robins TS, Diaz MO, Rowley JD, Blair DG, Vande Woude GF: The human met oncogene is related to the tyrosine kinase oncogenes. Nature. 1985 Nov 28-Dec 4;318(6044):385-8. 4069211
  9. Prat M, Narsimhan RP, Crepaldi T, Nicotra MR, Natali PG, Comoglio PM: The receptor encoded by the human c-MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors. Int J Cancer. 1991 Sep 30;49(3):323-8. 1917129
  10. Graziani A, Gramaglia D, Cantley LC, Comoglio PM: The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase. J Biol Chem. 1991 Nov 25;266(33):22087-90. 1718989
  11. Di Renzo MF, Narsimhan RP, Olivero M, Bretti S, Giordano S, Medico E, Gaglia P, Zara P, Comoglio PM: Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene. 1991 Nov;6(11):1997-2003. 1719465
  12. Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA: Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991 Feb 15;251(4995):802-4. 1846706
  13. Ferracini R, Longati P, Naldini L, Vigna E, Comoglio PM: Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinase. J Biol Chem. 1991 Oct 15;266(29):19558-64. 1655790
  14. Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, Giordano S, Graziani A, Panayotou G, Comoglio PM: A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell. 1994 Apr 22;77(2):261-71. 7513258
  15. Nusrat A, Parkos CA, Bacarra AE, Godowski PJ, Delp-Archer C, Rosen EM, Madara JL: Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium. J Clin Invest. 1994 May;93(5):2056-65. 8182137
  16. Boccaccio C, Ando M, Tamagnone L, Bardelli A, Michieli P, Battistini C, Comoglio PM: Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature. 1998 Jan 15;391(6664):285-8. 9440692
  17. Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, Swamy OR, Leone ME, Riedel H: Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol. 1999 Sep;19(9):6217-28. 10454568
  18. Wang D, Li Z, Messing EM, Wu G: Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM. J Biol Chem. 2002 Sep 27;277(39):36216-22. Epub 2002 Jul 29. 12147692
  19. Taher TE, Tjin EP, Beuling EA, Borst J, Spaargaren M, Pals ST: c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination. J Immunol. 2002 Oct 1;169(7):3793-800. 12244174
  20. Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, Tamagnone L, Comoglio PM: The semaphorin 4D receptor controls invasive growth by coupling with Met. Nat Cell Biol. 2002 Sep;4(9):720-4. 12198496
  21. Palka HL, Park M, Tonks NK: Hepatocyte growth factor receptor tyrosine kinase met is a substrate of the receptor protein-tyrosine phosphatase DEP-1. J Biol Chem. 2003 Feb 21;278(8):5728-35. Epub 2002 Dec 9. 12475979
  22. Wang D, Li Z, Schoen SR, Messing EM, Wu G: A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling. Biochem Biophys Res Commun. 2004 Jan 9;313(2):320-6. 14684163
  23. Higuchi T, Orita T, Katsuya K, Yamasaki Y, Akiyama K, Li H, Yamamoto T, Saito Y, Nakamura M: MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met. Mol Cell Biol. 2004 Sep;24(17):7456-68. 15314156
  24. Koch A, Mancini A, El Bounkari O, Tamura T: The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading. Oncogene. 2005 May 12;24(21):3436-47. 15735664
  25. Boccaccio C, Comoglio PM: Invasive growth: a MET-driven genetic programme for cancer and stem cells. Nat Rev Cancer. 2006 Aug;6(8):637-45. 16862193
  26. Sangwan V, Paliouras GN, Abella JV, Dube N, Monast A, Tremblay ML, Park M: Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase. J Biol Chem. 2008 Dec 5;283(49):34374-83. doi: 10.1074/jbc.M805916200. Epub 2008 Sep 26. 18819921
  27. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  28. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  29. Cao J, Shen C, Wang H, Shen H, Chen Y, Nie A, Yan G, Lu H, Liu Y, Yang P: Identification of N-glycosylation sites on secreted proteins of human hepatocellular carcinoma cells with a complementary proteomics approach. J Proteome Res. 2009 Feb;8(2):662-72. doi: 10.1021/pr800826u. 19196183
  30. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  31. Mahtouk K, Tjin EP, Spaargaren M, Pals ST: The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas. Biochim Biophys Acta. 2010 Dec;1806(2):208-19. doi: 10.1016/j.bbcan.2010.07.006. Epub 2010 Jul 22. 20655987
  32. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  33. Chaudhuri A, Xie MH, Yang B, Mahapatra K, Liu J, Marsters S, Bodepudi S, Ashkenazi A: Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET. J Biol Chem. 2011 Sep 16;286(37):32762-74. doi: 10.1074/jbc.M111.239384. Epub 2011 Jul 22. 21784853
  34. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  35. Schiering N, Casale E, Caccia P, Giordano P, Battistini C: Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex. Biochemistry. 2000 Nov 7;39(44):13376-82. 11063574
  36. Schiering N, Knapp S, Marconi M, Flocco MM, Cui J, Perego R, Rusconi L, Cristiani C: Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12654-9. Epub 2003 Oct 14. 14559966
  37. Kozlov G, Perreault A, Schrag JD, Park M, Cygler M, Gehring K, Ekiel I: Insights into function of PSI domains from structure of the Met receptor PSI domain. Biochem Biophys Res Commun. 2004 Aug 13;321(1):234-40. 15358240
  38. Stamos J, Lazarus RA, Yao X, Kirchhofer D, Wiesmann C: Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. EMBO J. 2004 Jun 16;23(12):2325-35. Epub 2004 May 27. 15167892
  39. Niemann HH, Jager V, Butler PJ, van den Heuvel J, Schmidt S, Ferraris D, Gherardi E, Heinz DW: Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. Cell. 2007 Jul 27;130(2):235-46. 17662939
  40. Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M, Allikmets R, Chidambaram A, Bergerheim UR, Feltis JT, Casadevall C, Zamarron A, Bernues M, Richard S, Lips CJ, Walther MM, Tsui LC, Geil L, Orcutt ML, Stackhouse T, Lipan J, Slife L, Brauch H, Decker J, Niehans G, Hughson MD, Moch H, Storkel S, Lerman MI, Linehan WM, Zbar B: Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet. 1997 May;16(1):68-73. 9140397
  41. Schmidt L, Junker K, Weirich G, Glenn G, Choyke P, Lubensky I, Zhuang Z, Jeffers M, Vande Woude G, Neumann H, Walther M, Linehan WM, Zbar B: Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. Cancer Res. 1998 Apr 15;58(8):1719-22. 9563489
  42. Lubensky IA, Schmidt L, Zhuang Z, Weirich G, Pack S, Zambrano N, Walther MM, Choyke P, Linehan WM, Zbar B: Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype. Am J Pathol. 1999 Aug;155(2):517-26. 10433944
  43. Park WS, Dong SM, Kim SY, Na EY, Shin MS, Pi JH, Kim BJ, Bae JH, Hong YK, Lee KS, Lee SH, Yoo NJ, Jang JJ, Pack S, Zhuang Z, Schmidt L, Zbar B, Lee JY: Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res. 1999 Jan 15;59(2):307-10. 9927037
  44. Olivero M, Valente G, Bardelli A, Longati P, Ferrero N, Cracco C, Terrone C, Rocca-Rossetti S, Comoglio PM, Di Renzo MF: Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family. Int J Cancer. 1999 Aug 27;82(5):640-3. 10417759
  45. Schmidt L, Junker K, Nakaigawa N, Kinjerski T, Weirich G, Miller M, Lubensky I, Neumann HP, Brauch H, Decker J, Vocke C, Brown JA, Jenkins R, Richard S, Bergerheim U, Gerrard B, Dean M, Linehan WM, Zbar B: Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene. 1999 Apr 8;18(14):2343-50. 10327054
  46. Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, Schmidt L, Zbar B, Vande Woude GF: A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene. 2000 Oct 12;19(43):4947-53. 11042681
  47. Kim IJ, Park JH, Kang HC, Shin Y, Lim SB, Ku JL, Yang HK, Lee KU, Park JG: A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer. J Med Genet. 2003 Aug;40(8):e97. 12920089
  48. Wang D, Li Z, Messing EM, Wu G: The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response element pathway. J Biol Chem. 2005 Apr 22;280(16):16393-401. Epub 2005 Feb 15. 15713673
  49. Campbell DB, Sutcliffe JS, Ebert PJ, Militerni R, Bravaccio C, Trillo S, Elia M, Schneider C, Melmed R, Sacco R, Persico AM, Levitt P: A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16834-9. Epub 2006 Oct 19. 17053076
  50. 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
  51. Stella GM, Benvenuti S, Gramaglia D, Scarpa A, Tomezzoli A, Cassoni P, Senetta R, Venesio T, Pozzi E, Bardelli A, Comoglio PM: MET mutations in cancers of unknown primary origin (CUPs). Hum Mutat. 2011 Jan;32(1):44-50. doi: 10.1002/humu.21374. Epub 2010 Nov 9. 20949619