RET proto-onkogen

RET
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2IVS, 2IVT, 2IVU, 2IVV, 2X2K, 2X2L, 2X2M, 2X2U, 4CKI, 4CKJ, 4UX8, 5AMN
Identifikatori
Aliasi	RET
Vanjski ID-jevi	OMIM: 164761 MGI: 97902 HomoloGene: 7517 GeneCards: RET
Lokacija gena (čovjek)
Hrom.	Hromosom 10 (čovjek)
Kraj	43,130,351 bp
Lokacija gena (miš)
Hrom.	Hromosom 6 (miš)
Kraj	118,174,679 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • calcium ion binding; • protein kinase activity; • kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • protein tyrosine kinase activity; • ATP binding; • signaling receptor activity; • transmembrane receptor protein tyrosine kinase activity; • Receptorska tirozin-kinaza; • transmembrane signaling receptor activity;
Ćelijska komponenta	• integral component of membrane; • endozom; • intracellular membrane-bounded organelle; • membrana; • receptor complex; • integral component of plasma membrane; • Akson; • soma; • dendrit; • early endosome; • Lipidni splav; • endosome membrane; • ćelijska membrana; • citosol; • plasma membrane protein complex; • citoplazma;
Biološki proces	• cellular response to retinoic acid; • ureteric bud development; • embryonic epithelial tube formation; • membrane protein proteolysis; • Fosforilacija; • transmembrane receptor protein tyrosine kinase signaling pathway; • positive regulation of cell migration; • neuron cell-cell adhesion; • nervous system development; • neuron maturation; • positive regulation of metanephric glomerulus development; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • regulation of axonogenesis; • protein phosphorylation; • enteric nervous system development; • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; • regulation of cell adhesion; • lymphocyte migration into lymphoid organs; • Ćelijska adhezija; • GO:1901313 positive regulation of gene expression; • ureter maturation; • response to pain; • retina development in camera-type eye; • neural crest cell migration; • neuron differentiation; • positive regulation of cell size; • positive regulation of neuron projection development; • posterior midgut development; • positive regulation of cell adhesion mediated by integrin; • innervation; • positive regulation of neuron maturation; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • GO:0072468 Transdukcija signala; • homophilic cell adhesion via plasma membrane adhesion molecules; • Peyer's patch morphogenesis; • peptidyl-tyrosine phosphorylation; • MAPK cascade; • axon guidance; • positive regulation of peptidyl-serine phosphorylation of STAT protein; • glial cell-derived neurotrophic factor receptor signaling pathway; • positive regulation of MAPK cascade; • positive regulation of protein kinase B signaling; • negative regulation of signal transduction; • Ćelijska diferencijacija; • negative regulation of apoptotic process; • positive regulation of ERK1 and ERK2 cascade; • neurogenesis;
	Izvori:Amigo / QuickGO
Ortolozi
	5979
	19713
	ENSG00000165731
	ENSMUSG00000030110
	P07949
	P35546
	NM_000323; NM_020629; NM_020630; NM_020975; NM_001355216
	NM_001080780; NM_009050
	NP_065681; NP_066124; NP_001342145; NP_066124.1
	NP_001074249; NP_033076
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

RET proto-onkogen kodira receptor tirozin-kinaze za članove porodice neurotrofnih faktora izvedenih iz glijske ćelijske linije) vanćelijskih signalnih molekula.^[5] Mutacije RET izazivaju gubitak funkcije povezane s razvojem Hirschsprungove bolesti, dok su mutajije pojačanja funkcije povezane sa razvojem različitih tipova ljudskog karcinoma, uključujući sržni karcinom štitnjače, multiplu endokrinu neoplaziju tipa 2A i 2B, feohromocitom i paratireoidnu hiperplaziju.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.114 aminokiselina, а molekulska težina 124.319 Da.^[6]

10	20	30	40	50
MAKATSGAAG	LRLLLLLLLP	LLGKVALGLY	FSRDAYWEKL	YVDQAAGTPL
LYVHALRDAP	EEVPSFRLGQ	HLYGTYRTRL	HENNWICIQE	DTGLLYLNRS
LDHSSWEKLS	VRNRGFPLLT	VYLKVFLSPT	SLREGECQWP	GCARVYFSFF
NTSFPACSSL	KPRELCFPET	RPSFRIRENR	PPGTFHQFRL	LPVQFLCPNI
SVAYRLLEGE	GLPFRCAPDS	LEVSTRWALD	REQREKYELV	AVCTVHAGAR
EEVVMVPFPV	TVYDEDDSAP	TFPAGVDTAS	AVVEFKRKED	TVVATLRVFD
ADVVPASGEL	VRRYTSTLLP	GDTWAQQTFR	VEHWPNETSV	QANGSFVRAT
VHDYRLVLNR	NLSISENRTM	QLAVLVNDSD	FQGPGAGVLL	LHFNVSVLPV
SLHLPSTYSL	SVSRRARRFA	QIGKVCVENC	QAFSGINVQY	KLHSSGANCS
TLGVVTSAED	TSGILFVNDT	KALRRPKCAE	LHYMVVATDQ	QTSRQAQAQL
LVTVEGSYVA	EEAGCPLSCA	VSKRRLECEE	CGGLGSPTGR	CEWRQGDGKG
ITRNFSTCSP	STKTCPDGHC	DVVETQDINI	CPQDCLRGSI	VGGHEPGEPR
GIKAGYGTCN	CFPEEEKCFC	EPEDIQDPLC	DELCRTVIAA	AVLFSFIVSV
LLSAFCIHCY	HKFAHKPPIS	SAEMTFRRPA	QAFPVSYSSS	GARRPSLDSM
ENQVSVDAFK	ILEDPKWEFP	RKNLVLGKTL	GEGEFGKVVK	ATAFHLKGRA
GYTTVAVKML	KENASPSELR	DLLSEFNVLK	QVNHPHVIKL	YGACSQDGPL
LLIVEYAKYG	SLRGFLRESR	KVGPGYLGSG	GSRNSSSLDH	PDERALTMGD
LISFAWQISQ	GMQYLAEMKL	VHRDLAARNI	LVAEGRKMKI	SDFGLSRDVY
EEDSYVKRSQ	GRIPVKWMAI	ESLFDHIYTT	QSDVWSFGVL	LWEIVTLGGN
PYPGIPPERL	FNLLKTGHRM	ERPDNCSEEM	YRLMLQCWKQ	EPDKRPVFAD
ISKDLEKMMV	KRRDYLDLAA	STPSDSLIYD	DGLSEEETPL	VDCNNAPLPR
ALPSTWIENK	LYGMSDPNWP	GESPVPLTRA	DGTNTGFPRY	PNDSVYANWM
LSPSAAKLMD	TFDS

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

Struktura

RET je skraćenica za rearanžiran tokom transfekcije, jer je prvobitno utvrđeno da je sekvenca DNK ovog gena preuređena unutar 3T3 fibroblastne ćelijske linije, nakon njene transfekcije sa DNK uzetom iz ljudskih limfomskih ćelija.^[7]

Ljudski gen RET je lokaliziran na hromosomu 10, sekvenca 10q11.2 i sadrži 21 egzon.^[8]

Prirodna alternativna prerada gena RET rezultira proizvodnjom tri različite izoforme proteina RET. RET51, RET43 i RET9 sadrže 51, 43 i 9 aminokiselina u repu C-terminala.^[9] Biološke uloge izoformi RET51 i RET9 su najbolje proučene in vivo, jer su to najčešće izoforme u kojima se javlja RET.

Zajednička za sve izoforme je struktura domena. Svaki protein podijeljen je u tri domena: N-terminalni vanćelijski domenu s četiri kadherin slična ponavljanja i cisteinom bogata regija, hidrofobni transmembranski domen i domen citoplazmatske tirozin kinaze, koji je podeljen insercijom 27 aminokiselina. Unutar citoplazmatskog tirozin-kinaznog domena postoji 16 tirozina (Tyr) u RET9 i 18 u RET51. Tyr1090 i Tyr1096 prisutni su samo u izoformi RET51.^[10]

Vanćelijski domen RET-a sadrži devet mjesta N-glikolizacije. Prijavljeno je da potpuno glikozilirani RET protein ima molekulsku težinu od 170 kDa, iako nije jasno na koji izoformu se odnosi ova molekulska masa.^[11]

Aktivacija kinaze

RET je receptor za ligand porodice GDNF (GFL).^[12]

Da bi aktivirali RET, GFL-i prvo moraju formirati kompleks sa glikozilfosfatidilinozitolski (GPI) usidreni koreceptor. Sami koreceptori su klasificirani kao članovi proteinske porodice GDNF receptor-α (GFRα). Različiti članovi porodice GFRα (GFRα1, GFRα2, GFRα3, GFRα4) pokazuju specifičnu aktivnost vezivanja za određene GFL-ove.^[13] Nakon formiranja kompleksa GFL-GFRα, on okuplja dvije molekule RET-a, pokrećući trans-autofosforilaciju specifičnih tirozinskih ostataka unutar tirozin-kinaznog domena svake molekule RET-a. Pokazalo se da su Tyr900 i Tyr905 unutar aktivacijske petlje (A-petlje) kinaznog domena autofosforilziraju mjesta masene spektrometrije.^[14] Fosforilacija Tyr905 stabilizira aktivnu konformaciju kinaze, što zauzvrat rezultira autofosforilacijom drugih ostataka tirozina koji se uglavnom nalaze u C-terminalnoj repnoj regiji molekule.^[10]

Snimak kristalne strukture RET-dimera http://www.pdb.org/pdb/explore.do?structureId=2IVT 2IVT

Struktura prikazana lijevo preuzeta je iz koda banke proteinskih podataka 2IVT.^[5] Struktura je dimera formiran između dvije proteinske molekule, od kojih svaki obuhvata aminokiseline 703-1012 molekula RET-a, pokrivajući RET-ov unutarćelijski tirozin-kinazni domen. Jedna molekula proteina, molekula A prikazana je žutom bojom, a druga, molekula B sivom. Aktivacijska petlja obojena je ljubičasto, a odabrani ostaci tirozina zelenom bojom. Dio aktivacijske petlje iz molekula B je odsutan.

Fosforilacija Tyr981 i dodatnih tirozina Tyr1015, Tyr1062 i Tyr1096, koji nisu obuhvaćeni gore navedenom strukturom, pokazalo se da su važni za pokretanje unutarćelijskih transdukcija signala.

Uloga RET signalizacije tokom razvoja

Miševi koji imaju nedostatak GDNF -a, GFRα1 ili samog RET-proteina pokazuju ozbiljne nedostatke u razvoju bubrega i utrobnog nervnog sistema. Ovo implicira transdukciju RET signala kao ključ za razvoj normalnih bubrega i enternog nervnog sistema.^[10]

Klinički značaj

Aktiviranje tačkastih mutacija u RET -u može dovesti do sindroma nasljednog raka poznatog kao multipla endokrina neoplazija tip 2 (MEN 2).^[15] Postoje tri podtipa zasnovana na kliničkoj slici: MEN 2A, MEN 2B i porodični sržnii karcinom štitnjače (FMTC).^[16] Postoji visok stepen korelacije između položaja tačkaste mutacije i fenotipa bolesti.

Hromosomska preuređenja koja generiraju fuzijski gen, što rezultira jukstapozicijom C-terminalne regije RET proteina s N-terminalnim dijelom drugog proteina, također mogu dovesti do konstitutivne aktivacije RET-kinaze. Ovaj tip preuređenja prvenstveno je povezan s papilnim karcinomom štitnjače (PTC) gdje predstavljaj 10-20% slučajeva i nemaloćelijskog karcinoma pluća (NSCLC), gdje predstavljaj 2% slučajeva. U literaturi je opisano nekoliko fuzijskih partnera, a najčešći za oba tipa raka uključuju KIF5B, CCDC6 i NCOA4.

Dok su stariji inhibitori multikinaza, poput kabozantiniba ili vandetaniba, pokazali skromnu učinkovitost u ciljanju malignih bolesti uzrokovanih RET-om, noviji selektivni inhibitori (poput selpercatiniba i pralsetiniba) pokazali su značajnu aktivnost i mutacije i fuzije. Rezultati ispitivanja LIBRETTO-001, koji je proučavao selpercatinib pokazali su preživljavanje bez progresije od 17,5 mjeseci u prethodno liječenom RET-pozitivnom NSCLC-u i 22 mjeseca za RET-pozitivni karcinom štitnjače, što je dovelo do odobrenja FDA za obje ove indikacije u maju 2020. Nekoliko drugih selektivnih inhibitora RET-a je u razvoju, uključujući TPX-0046, makrociklični inhibitor RET-a i Src namijenjen inhibiranju mutacija i pružajući otpornost na trenutne inhibitore.

Baze podataka o bolestima

Genska varijanta [http://www.arup.utah.edu/database/MEN2/MEN2_welcome.php RET baze podataka na University of Utah, identificirala je (ovembra 2014) 166 mutacija kojr su uključene u MEN2.

Interakcije

RET proto-onkogen je pokazao interakcije sa:

DOK1,^[17]
DOK5,^[18]^[19]
GDNF,^[20]^[21]
GRB10,^[22]
GRB7,^[23]
Grb2,^[22]^[24]
SHC1,^[24]^[25] i
STAT3.^[26]^[27]^[28]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000165731 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030110 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Knowles PP, Murray-Rust J, Kjaer S, et al. (2006). "Structure and chemical inhibition of the RET tyrosine kinase domain". J. Biol. Chem. 281 (44): 33577–87. doi:10.1074/jbc.M605604200. PMID 16928683.
^ "UniProt, P07949". Pristupljeno 4. 9. 2021.
^ Takahashi M, Ritz J, Cooper GM (1985). "Activation of a novel human transforming gene, ret, by DNA rearrangement". Cell. 42 (2): 581–8. doi:10.1016/0092-8674(85)90115-1. PMID 2992805. S2CID 13567823.
^ Ceccherini I, Bocciardi R, Luo Y, et al. (1993). "Exon structure and flanking intronic sequences of the human RET proto-oncogene". Biochem. Biophys. Res. Commun. 196 (3): 1288–1295. doi:10.1006/bbrc.1993.2392. PMID 7902707.
^ Myers SM, Eng C, Ponder BA, et al. (1995). "Characterization of RET proto-oncogene 3' splicing variants and polyadenylation sites: a novel C-terminus for RET". Oncogene. 11 (10): 2039–2045. PMID 7478523.
^ ^a ^b ^c Arighi E, Borrello MG, Sariola H (2005). "RET tyrosine kinase signaling in development and cancer". Cytokine Growth Factor Rev. 16 (4–5): 441–67. doi:10.1016/j.cytogfr.2005.05.010. PMID 15982921.
^ Takahashi M, Asai N, Iwashita T, et al. (1993). "Characterization of the ret proto-oncogene products expressed in mouse L cells". Oncogene. 8 (11): 2925–2929. PMID 8414495.
^ Baloh RH, Enomoto H, Johnson EM, et al. (2000). "The GDNF family ligands and receptors - implications for neural development". Curr. Opin. Neurobiol. 10 (1): 103–10. doi:10.1016/S0959-4388(99)00048-3. PMID 10679429. S2CID 32315320.
^ Airaksinen MS, Titievsky A, Saarma M (1999). "GDNF family neurotrophic factor signaling: four masters, one servant?". Mol. Cell. Neurosci. 13 (5): 313–25. doi:10.1006/mcne.1999.0754. PMID 10356294. S2CID 46427535.
^ Kawamoto Y, Takeda K, Okuno Y, et al. (2004). "Identification of RET autophosphorylation sites by mass spectrometry". J. Biol. Chem. 279 (14): 14213–24. doi:10.1074/jbc.M312600200. PMID 14711813.
^ OMIM: MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA; MEN2A -171400
^ Qi XP, Ma JM, Du ZF, Ying RB, Fei J, Jin HY, Han JS, Wang JQ, Chen XL, Chen CY, Liu WT, Lu JJ, Zhang JG, Zhang XN (2011). "RET germline mutations identified by exome sequencing in a Chinese multiple endocrine neoplasia type 2A/familial medullary thyroid carcinoma family". PLOS ONE. 6 (5): e20353. Bibcode:2011PLoSO...620353Q. doi:10.1371/journal.pone.0020353. PMC 3105051. PMID 21655256.
^ Murakami H, Yamamura Y, Shimono Y, Kawai K, Kurokawa K, Takahashi M (septembar 2002). "Role of Dok1 in cell signaling mediated by RET tyrosine kinase". J. Biol. Chem. 277 (36): 32781–90. doi:10.1074/jbc.M202336200. PMID 12087092.
^ Crowder RJ, Enomoto H, Yang M, Johnson EM, Milbrandt J (oktobar 2004). "Dok-6, a Novel p62 Dok family member, promotes Ret-mediated neurite outgrowth". J. Biol. Chem. 279 (40): 42072–81. doi:10.1074/jbc.M403726200. PMID 15286081.
^ Grimm J, Sachs M, Britsch S, Di Cesare S, Schwarz-Romond T, Alitalo K, Birchmeier W (juli 2001). "Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation" (PDF). J. Cell Biol. 154 (2): 345–54. doi:10.1083/jcb.200102032. PMC 2150770. PMID 11470823.
^ Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M, Rosenthal A (juni 1997). "A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor". Nature. 387 (6634): 717–21. doi:10.1038/42722. PMID 9192898. S2CID 4360246.
^ Cik M, Masure S, Lesage AS, Van Der Linden I, Van Gompel P, Pangalos MN, Gordon RD, Leysen JE (septembar 2000). "Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions". J. Biol. Chem. 275 (36): 27505–12. doi:10.1074/jbc.M000306200. PMID 10829012.
^ ^a ^b Pandey A, Duan H, Di Fiore PP, Dixit VM (septembar 1995). "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): 21461–3. doi:10.1074/jbc.270.37.21461. PMID 7665556.
^ Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM (maj 1996). "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7". J. Biol. Chem. 271 (18): 10607–10. doi:10.1074/jbc.271.18.10607. PMID 8631863.
^ ^a ^b Borrello MG, Pelicci G, Arighi E, De Filippis L, Greco A, Bongarzone I, Rizzetti M, Pelicci PG, Pierotti MA (juni 1994). "The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins". Oncogene. 9 (6): 1661–8. PMID 8183561.
^ Arighi E, Alberti L, Torriti F, Ghizzoni S, Rizzetti MG, Pelicci G, Pasini B, Bongarzone I, Piutti C, Pierotti MA, Borrello MG (februar 1997). "Identification of Shc docking site on Ret tyrosine kinase". Oncogene. 14 (7): 773–82. doi:10.1038/sj.onc.1200896. PMID 9047384.
^ Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB, Chin YE (novembar 2004). "Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells". Mol. Cell. Biol. 24 (21): 9390–400. doi:10.1128/MCB.24.21.9390-9400.2004. PMC 522220. PMID 15485908.
^ Hwang JH, Kim DW, Suh JM, Kim H, Song JH, Hwang ES, Park KC, Chung HK, Kim JM, Lee TH, Yu DY, Shong M (juni 2003). "Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thyroid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation". Mol. Endocrinol. 17 (6): 1155–66. doi:10.1210/me.2002-0401. PMID 12637586.
^ Schuringa JJ, Wojtachnio K, Hagens W, Vellenga E, Buys CH, Hofstra R, Kruijer W (august 2001). "MEN2A-RET-induced cellular transformation by activation of STAT3". Oncogene. 20 (38): 5350–8. doi:10.1038/sj.onc.1204715. PMID 11536047.

Dopunska literatura

Eng C, Mulligan LM (1997). "Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and hirschsprung disease". Hum. Mutat. 9 (2): 97–109. doi:10.1002/(SICI)1098-1004(1997)9:2<97::AID-HUMU1>3.0.CO;2-M. PMID 9067749.
Hofstra RM, Osinga J, Buys CH (1998). "Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype". Eur. J. Hum. Genet. 5 (4): 180–5. doi:10.1159/000484760. PMID 9359036.
Nikiforov YE (2002). "RET/PTC rearrangement in thyroid tumors". Endocr. Pathol. 13 (1): 3–16. doi:10.1385/EP:13:1:03. PMID 12114746. S2CID 23964165.
Santoro M, Melillo RM, Carlomagno F, et al. (2004). "Minireview: RET: normal and abnormal functions". Endocrinology. 145 (12): 5448–5451. doi:10.1210/en.2004-0922. PMID 15331579.
Santoro M, Carlomagno F, Melillo RM, Fusco A (2005). "Dysfunction of the RET receptor in human cancer". Cell. Mol. Life Sci. 61 (23): 2954–2964. doi:10.1007/s00018-004-4276-8. PMID 15583857.
Niccoli-Sire P, Conte-Devolx B (2005). "[RET mutations and preventive treatment of medullary thyroid cancer]". Ann. Endocrinol. 66 (3): 168–75. doi:10.1016/s0003-4266(05)81748-2. PMID 15988377.
Lantieri F, Griseri P, Ceccherini I (2006). "Molecular mechanisms of RET-induced Hirschsprung pathogenesis". Ann. Med. 38 (1): 11–9. doi:10.1080/07853890500442758. PMID 16448984. S2CID 43686346.
Ciampi R, Nikiforov YE (2007). "RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis". Endocrinology. 148 (3): 936–41. doi:10.1210/en.2006-0921. PMID 16946010.
Plaza-Menacho I, Burzynski GM, de Groot JW, et al. (2007). "Current concepts in RET-related genetics, signaling and therapeutics" (PDF). Trends Genet. 22 (11): 627–36. doi:10.1016/j.tig.2006.09.005. PMID 16979782.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Multiple Endocrine Neoplasia Type 2
ret Proto-Oncogene Proteins na US National Library of Medicine Medical Subject Headings (MeSH)

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000165731 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030110 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[knowles-5] Knowles PP, Murray-Rust J, Kjaer S, et al. (2006). "Structure and chemical inhibition of the RET tyrosine kinase domain". J. Biol. Chem. 281 (44): 33577–87. doi:10.1074/jbc.M605604200. PMID 16928683.

[UniProt-6] "UniProt, P07949". Pristupljeno 4. 9. 2021.

[takahasi-7] Takahashi M, Ritz J, Cooper GM (1985). "Activation of a novel human transforming gene, ret, by DNA rearrangement". Cell. 42 (2): 581–8. doi:10.1016/0092-8674(85)90115-1. PMID 2992805. S2CID 13567823.

[ceccherini-8] Ceccherini I, Bocciardi R, Luo Y, et al. (1993). "Exon structure and flanking intronic sequences of the human RET proto-oncogene". Biochem. Biophys. Res. Commun. 196 (3): 1288–1295. doi:10.1006/bbrc.1993.2392. PMID 7902707.

[myers-9] Myers SM, Eng C, Ponder BA, et al. (1995). "Characterization of RET proto-oncogene 3' splicing variants and polyadenylation sites: a novel C-terminus for RET". Oncogene. 11 (10): 2039–2045. PMID 7478523.

[arighi-10] Arighi E, Borrello MG, Sariola H (2005). "RET tyrosine kinase signaling in development and cancer". Cytokine Growth Factor Rev. 16 (4–5): 441–67. doi:10.1016/j.cytogfr.2005.05.010. PMID 15982921.

[takahashi-11] Takahashi M, Asai N, Iwashita T, et al. (1993). "Characterization of the ret proto-oncogene products expressed in mouse L cells". Oncogene. 8 (11): 2925–2929. PMID 8414495.

[baloh-12] Baloh RH, Enomoto H, Johnson EM, et al. (2000). "The GDNF family ligands and receptors - implications for neural development". Curr. Opin. Neurobiol. 10 (1): 103–10. doi:10.1016/S0959-4388(99)00048-3. PMID 10679429. S2CID 32315320.

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[15] OMIM: MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA; MEN2A -171400

[pmid21655256-16] Qi XP, Ma JM, Du ZF, Ying RB, Fei J, Jin HY, Han JS, Wang JQ, Chen XL, Chen CY, Liu WT, Lu JJ, Zhang JG, Zhang XN (2011). "RET germline mutations identified by exome sequencing in a Chinese multiple endocrine neoplasia type 2A/familial medullary thyroid carcinoma family". PLOS ONE. 6 (5): e20353. Bibcode:2011PLoSO...620353Q. doi:10.1371/journal.pone.0020353. PMC 3105051. PMID 21655256.

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[pmid9192898-20] Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M, Rosenthal A (juni 1997). "A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor". Nature. 387 (6634): 717–21. doi:10.1038/42722. PMID 9192898. S2CID 4360246.

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