FLT1
Receptor 1 vaskularnog endotelnog faktora rasta je protein koji je kod ljudi kodiran genom FLT1.[5]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.338 aminokiselina, a molekulska težina 150 769 Da .[6]
- Simboli
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
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MVSYWDTGVL | LCALLSCLLL | TGSSSGSKLK | DPELSLKGTQ | HIMQAGQTLH | ||||
LQCRGEAAHK | WSLPEMVSKE | SERLSITKSA | CGRNGKQFCS | TLTLNTAQAN | ||||
HTGFYSCKYL | AVPTSKKKET | ESAIYIFISD | TGRPFVEMYS | EIPEIIHMTE | ||||
GRELVIPCRV | TSPNITVTLK | KFPLDTLIPD | GKRIIWDSRK | GFIISNATYK | ||||
EIGLLTCEAT | VNGHLYKTNY | LTHRQTNTII | DVQISTPRPV | KLLRGHTLVL | ||||
NCTATTPLNT | RVQMTWSYPD | EKNKRASVRR | RIDQSNSHAN | IFYSVLTIDK | ||||
MQNKDKGLYT | CRVRSGPSFK | SVNTSVHIYD | KAFITVKHRK | QQVLETVAGK | ||||
RSYRLSMKVK | AFPSPEVVWL | KDGLPATEKS | ARYLTRGYSL | IIKDVTEEDA | ||||
GNYTILLSIK | QSNVFKNLTA | TLIVNVKPQI | YEKAVSSFPD | PALYPLGSRQ | ||||
ILTCTAYGIP | QPTIKWFWHP | CNHNHSEARC | DFCSNNEESF | ILDADSNMGN | ||||
RIESITQRMA | IIEGKNKMAS | TLVVADSRIS | GIYICIASNK | VGTVGRNISF | ||||
YITDVPNGFH | VNLEKMPTEG | EDLKLSCTVN | KFLYRDVTWI | LLRTVNNRTM | ||||
HYSISKQKMA | ITKEHSITLN | LTIMNVSLQD | SGTYACRARN | VYTGEEILQK | ||||
KEITIRDQEA | PYLLRNLSDH | TVAISSSTTL | DCHANGVPEP | QITWFKNNHK | ||||
IQQEPGIILG | PGSSTLFIER | VTEEDEGVYH | CKATNQKGSV | ESSAYLTVQG | ||||
TSDKSNLELI | TLTCTCVAAT | LFWLLLTLFI | RKMKRSSSEI | KTDYLSIIMD | ||||
PDEVPLDEQC | ERLPYDASKW | EFARERLKLG | KSLGRGAFGK | VVQASAFGIK | ||||
KSPTCRTVAV | KMLKEGATAS | EYKALMTELK | ILTHIGHHLN | VVNLLGACTK | ||||
QGGPLMVIVE | YCKYGNLSNY | LKSKRDLFFL | NKDAALHMEP | KKEKMEPGLE | ||||
QGKKPRLDSV | TSSESFASSG | FQEDKSLSDV | EEEEDSDGFY | KEPITMEDLI | ||||
SYSFQVARGM | EFLSSRKCIH | RDLAARNILL | SENNVVKICD | FGLARDIYKN | ||||
PDYVRKGDTR | LPLKWMAPES | IFDKIYSTKS | DVWSYGVLLW | EIFSLGGSPY | ||||
PGVQMDEDFC | SRLREGMRMR | APEYSTPEIY | QIMLDCWHRD | PKERPRFAEL | ||||
VEKLGDLLQA | NVQQDGKDYI | PINAILTGNS | GFTYSTPAFS | EDFFKESISA | ||||
PKFNSGSSDD | VRYVNAFKFM | SLERIKTFEE | LLPNATSMFD | DYQGDSSTLL | ||||
ASPMLKRFTW | TDSKPKASLK | IDLRVTSKSK | ESGLSDVSRP | SFCHSSCGHV | ||||
SEGKRRFTYD | HAELERKIAC | CSPPPDYNSV | VLYSTPPI |
Funkcija
urediOnkogen FLT pripada porodici src gena i srodan je onkogenu ROS (MIM 165020). Kao i drugi članovi ove porodice, pokazuje aktivnost tirozinske protein-kinaze, koja je važna za kontrolu proliferacije i diferencijacije ćelija. Struktura sekvence gena FLT nalikuje strukturi gena FMS (MIM 164770); stoga, Yoshida et al. (1987) predložili su naziv FLT kao akronim za FMS-sličnu tirozin-kinazu.[7]
Nedavno je otkriveno da je ablacija VEGFR1 hemijskim i genetičkim putem povećala pretvorbu bijelog masnog tkiva u tamno masno tkivo, kao i povećala smeđu masnu angiogenezu kod miševa.[8]
Utvrđeno je da funkcionalne genetičke varijacije u FLT1 (rs9582036) utiču na preživljavanje karcinom pluća ne-malih ćelija.[9]
Interakcije
urediPokazano je da FLT1 stupa u interakcije sa PLCG1 [10] i VEGF-B.[11][12]
Također pogledajte
urediReference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000102755 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029648 - 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.
- ^ Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M (april 1990). "Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family". Oncogene. 5 (4): 519–24. PMID 2158038.
- ^ "UniProt, P17948". Pristupljeno 11. 9. 2017.
- ^ "Entrez Gene: FLT1 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)".
- ^ Seki T, Hosaka K, Fischer C, Lim S, Andersson P, Abe M, Iwamoto H, Gao Y, Wang X, Fong GH, Cao Y (februar 2018). "Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning". The Journal of Experimental Medicine. 215 (2): 611–626. doi:10.1084/jem.20171012. PMC 5789413. PMID 29305395.
- ^ Glubb DM, Paré-Brunet L, Jantus-Lewintre E, Jiang C, Crona D, Etheridge AS, Mirza O, Zhang W, Seiser EL, Rzyman W, Jassem J, Auman T, Hirsch FR, Owzar K, Camps C, Dziadziuszko R, Innocenti F (juli 2015). "Functional FLT1 Genetic Variation is a Prognostic Factor for Recurrence in Stage I-III Non-Small-Cell Lung Cancer". Journal of Thoracic Oncology. 10 (7): 1067–75. doi:10.1097/JTO.0000000000000549. PMC 4494119. PMID 26134224.
- ^ Cunningham SA, Arrate MP, Brock TA, Waxham MN (novembar 1997). "Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites". Biochemical and Biophysical Research Communications. 240 (3): 635–9. doi:10.1006/bbrc.1997.7719. PMID 9398617.
- ^ Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U (septembar 1998). "Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11709–14. doi:10.1073/pnas.95.20.11709. PMC 21705. PMID 9751730.
- ^ Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K (juli 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry. 274 (30): 21217–22. doi:10.1074/jbc.274.30.21217. PMID 10409677.
Dopunska literatura
uredi- Petrova TV, Makinen T, Alitalo K (novembar 1999). "Signaling via vascular endothelial growth factor receptors". Experimental Cell Research. 253 (1): 117–30. doi:10.1006/excr.1999.4707. PMID 10579917.
- Sato Y, Kanno S, Oda N, Abe M, Ito M, Shitara K, Shibuya M (maj 2000). "Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction". Annals of the New York Academy of Sciences. 902 (1): 201–5, discussion 205–7. doi:10.1111/j.1749-6632.2000.tb06314.x. PMID 10865839.
- Boyd AW, Lackmann M (decembar 2001). "Signals from Eph and ephrin proteins: a developmental tool kit". Science's STKE. 2001 (112): re20. doi:10.1126/stke.2001.112.re20. PMID 11741094.
- Luttun A, Tjwa M, Carmeliet P (decembar 2002). "Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic _targets for angiogenic disorders". Annals of the New York Academy of Sciences. 979: 80–93. doi:10.1111/j.1749-6632.2002.tb04870.x. PMID 12543719.
- Maynard SE, Venkatesha S, Thadhani R, Karumanchi SA (maj 2005). "Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia". Pediatric Research. 57 (5 Pt 2): 1R–7R. doi:10.1203/01.PDR.0000159567.85157.B7. PMID 15817508.
- Shibuya M (2007). "Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis". Angiogenesis. 9 (4): 225–30, discussion 231. doi:10.1007/s10456-006-9055-8. PMID 17109193.
- Widmer M, Villar J, Benigni A, Conde-Agudelo A, Karumanchi SA, Lindheimer M (januar 2007). "Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review". Obstetrics and Gynecology. 109 (1): 168–80. doi:10.1097/01.AOG.0000249609.04831.7c. PMID 17197602.
- López-Novoa JM (mart 2007). "Soluble endoglin is an accurate predictor and a pathogenic molecule in pre-eclampsia". Nephrology, Dialysis, Transplantation. 22 (3): 712–4. doi:10.1093/ndt/gfl768. PMID 17210583.
- Poesen K, Lambrechts D, Van Damme P, Dhondt J, Bender F, Frank N, Bogaert E, Claes B, Heylen L, Verheyen A, Raes K, Tjwa M, Eriksson U, Shibuya M, Nuydens R, Van Den Bosch L, Meert T, D'Hooge R, Sendtner M, Robberecht W, Carmeliet P (oktobar 2008). "Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration". The Journal of Neuroscience. 28 (42): 10451–9. doi:10.1523/JNEUROSCI.1092-08.2008. PMID 18923022.
- Joukov V, Kaipainen A, Jeltsch M, Pajusola K, Olofsson B, Kumar V, Eriksson U, Alitalo K (novembar 1997). "Vascular endothelial growth factors VEGF-B and VEGF-C". Journal of Cellular Physiology. 173 (2): 211–5. doi:10.1002/(SICI)1097-4652(199711)173:2<211::AID-JCP23>3.0.CO;2-H. PMID 9365524.
- Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (decembar 2005). "VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche". Nature. 438 (7069): 820–7. doi:10.1038/nature04186. PMC 2945882. PMID 16341007.