TrkA receptor

Neurotrofna tirozinska kinaza, receptor, tip 1
	; PDB prikaz baziran na 1he7.
Dostupne strukture
	1HE7, 1SHC, 1WWA, 1WWW, 2IFG, 4AOJ, 4F0I, 4GT5
Identifikatori
Simboli	NTRK1; MTC; TRK; TRK1; TRKA; Trk-A; p140-TrkA
Vanjski ID	OMIM: 191315 MGI: 97383 HomoloGene: 1898 GeneCards: NTRK1 Gene
EC broj	2.7.10.1
Ontologija gena
Molekulska funkcija	• aktivnost transmembranske receptorske proteinske tirozinske kinaze; • vezivanje neurotrofnog p75 receptora; • proteinsko vezivanje;
Ćelijska komponenta	• endozom; • rani endozom; • kasni endozom;
Biološki proces	• aktivacija MAPKK aktivnosti; • proteinska fosforilacija; • signalni put transmembranske receptorske proteinske tirozinske kinaze;
Pregled RNK izražavanja
	podaci
Ortolozi

edit

Receptor nervnog faktora rasta visokog afiniteta (engl. High affinity nerve growth factor receptor; neurotrofni tirozinski kinazni receptor tipa 1, TRK1-transformišući tirozinski kinazni protein, Trk-A) protein je koji je kod ljudi kodiran NTRK1 genom.^[1]

Ovaj gen kodira člana familije neurotrofnih tirozinskih kinaznih receptora (NTKR). Ova kinaza je za membranu vezani receptor koji, nakon neurotrofinskog vezivanje, fosforiliše sebe (autofosforilacija) i članove MAPK puta. Prisustvo ove kinaze dovodi do ćelijske diferencijacije i može da ima ulogu u specificiranju senzornih neuronskih podtipova. Mutacije ovog gena su vezane za kongenitalnu insenzitivnost na bol sa anhidrozom, samo povređivanje, mentalnu retardaciju i kancer. Alternativne transkriptne splajsne varijante ovog gena su poznate, ali su samo tri do sada okarakterisane.^[2]

Interakcije

TrkA formira interakcije sa:

Abl gen.^[3]^[4]
FRS2,^[5]
Grb2,^[6]^[7]
MATK,^[8]
NGFB,^[9]^[10]^[11]
PLCG1,^[3]^[5]^[12]^[13]
RICS,^[14]
SQSTM1,^[15]^[16]^[17]^[18]
SH2B1,^[3]^[13]
SH2B2,^[13] and
SHC1.^[3]^[5]^[13]^[14]^[19]

Mali molekuli kao što su amitriptilin i derivat gamboginske kiseline aktiviraju TrkA. Amitriptilin aktivira TrkA i omogućava heterodimerizaciju TrkA i TrkB u odsustvu NGF. Do vezivanja amitriptilina za TrkA dolazi u leucinom bogatom regionu (LRR) ekstracelularnog domena receptora, koji je udaljen od NGF mesta vezivanje. Amitriptilin poseduje neurotrono dejstvo in-vitro i in-vivo (mišji model).^[20] Gamboginski amid, derivat gamboginske kiseline, selektivno aktivira TrkA (a ne aktivira TrkB i TrkC) in-vitro i in-vivo putem interakcije sa citoplazmatičnim domenom u blizini membrane.^[21]

Reference

↑ Martin-Zanca D, Hughes SH, Barbacid M (April 1986). „A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences”. Nature 319 (6056): 743–8. DOI:10.1038/319743a0. PMID 2869410.
↑ „Entrez Gene: NTRK1 neurotrophic tyrosine kinase, receptor, type 1”.
↑ ^3,0 ^3,1 ^3,2 ^3,3 Koch, A; Mancini A; Stefan M; Niedenthal R; Niemann H; Tamura T (March 2000). „Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop”. FEBS Lett. 469 (1): 72–6. DOI:10.1016/S0014-5793(00)01242-4. PMID 10708759.
↑ Yano, H; Cong F; Birge R B; Goff S P; Chao M V (February 2000). „Association of the Abl tyrosine kinase with the Trk nerve growth factor receptor”. J. Neurosci. Res. 59 (3): 356–64. DOI:10.1002/(SICI)1097-4547(20000201)59:3<356::AID-JNR9>3.0.CO;2-G. PMID 10679771.
↑ ^5,0 ^5,1 ^5,2 Meakin, S O; MacDonald J I; Gryz E A; Kubu C J; Verdi J M (April 1999). „The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation”. J. Biol. Chem. 274 (14): 9861–70. DOI:10.1074/jbc.274.14.9861. PMID 10092678.
↑ Song, Cheng; Perides George; Liu Ya Fang (February 2002). „Expression of full-length polyglutamine-expanded Huntingtin disrupts growth factor receptor signaling in rat pheochromocytoma (PC12) cells”. J. Biol. Chem. 277 (8): 6703–7. DOI:10.1074/jbc.M110338200. PMID 11733534.
↑ MacDonald, J I; Gryz E A; Kubu C J; Verdi J M; Meakin S O (June 2000). „Direct binding of the signaling adapter protein Grb2 to the activation loop tyrosines on the nerve growth factor receptor tyrosine kinase, TrkA”. J. Biol. Chem. 275 (24): 18225–33. DOI:10.1074/jbc.M001862200. PMID 10748052.
↑ Yamashita, H; Avraham S; Jiang S; Dikic I; Avraham H (May 1999). „The Csk homologous kinase associates with TrkA receptors and is involved in neurite outgrowth of PC12 cells”. J. Biol. Chem. 274 (21): 15059–65. DOI:10.1074/jbc.274.21.15059. PMID 10329710.
↑ Nykjaer, Anders; Lee Ramee, Teng Kenneth K, Jansen Pernille, Madsen Peder, Nielsen Morten S, Jacobsen Christian, Kliemannel Marco, Schwarz Elisabeth, Willnow Thomas E, Hempstead Barbara L, Petersen Claus M (February 2004). „Sortilin is essential for proNGF-induced neuronal cell death”. Nature 427 (6977): 843–8. DOI:10.1038/nature02319. PMID 14985763.
↑ Lee, R; Kermani P; Teng K K; Hempstead B L (November 2001). „Regulation of cell survival by secreted proneurotrophins”. Science 294 (5548): 1945–8. DOI:10.1126/science.1065057. PMID 11729324.
↑ Wiesmann, C; Ultsch M H; Bass S H; de Vos A M (September 1999). „Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor”. Nature 401 (6749): 184–8. DOI:10.1038/43705. PMID 10490030.
↑ Ohmichi, M; Decker S J; Pang L; Saltiel A R (August 1991). „Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1”. Biochem. Biophys. Res. Commun. 179 (1): 217–23. DOI:10.1016/0006-291X(91)91357-I. PMID 1715690.
↑ ^13,0 ^13,1 ^13,2 ^13,3 Qian, X; Riccio A; Zhang Y; Ginty D D (November 1998). „Identification and characterization of novel substrates of Trk receptors in developing neurons”. Neuron 21 (5): 1017–29. DOI:10.1016/S0896-6273(00)80620-0. PMID 9856458.
↑ ^14,0 ^14,1 Nakamura, Takeshi; Komiya Misako; Sone Kiyoaki; Hirose Eiji; Gotoh Noriko; Morii Hiroshi; Ohta Yasutaka; Mori Nozomu (December 2002). „Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules”. Mol. Cell. Biol. 22 (24): 8721–34. DOI:10.1128/MCB.22.24.8721-8734.2002. PMC 139861. PMID 12446789.
↑ Wooten, M W; Seibenhener M L; Mamidipudi V; Diaz-Meco M T; Barker P A; Moscat J (March 2001). „The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor”. J. Biol. Chem. 276 (11): 7709–12. DOI:10.1074/jbc.C000869200. PMID 11244088.
↑ Geetha T, Wooten MW (February 2003). „Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling”. J. Biol. Chem. 278 (7): 4730–9. DOI:10.1074/jbc.M208468200. PMID 12471037.
↑ Jadhav T, Geetha T, Jiang J, Wooten MW (July 2008). „Identification of a consensus site for TRAF6/p62 polyubiquitination”. Biochem. Biophys. Res. Commun. 371 (3): 521–4. DOI:10.1016/j.bbrc.2008.04.138. PMC 2474794. PMID 18457658.
↑ Wooten MW, Geetha T, Babu JR, Seibenhener ML, Peng J, Cox N, Diaz-Meco MT, Moscat J (March 2008). „Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins”. J. Biol. Chem. 283 (11): 6783–9. DOI:10.1074/jbc.M709496200. PMID 18174161.
↑ Borrello, M G; Pelicci G; Arighi E; De Filippis L; Greco A; Bongarzone I; Rizzetti M; Pelicci P G i dr.. (June 1994). „The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins”. Oncogene 9 (6): 1661–8. PMID 8183561.
↑ Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K. (June 2009). „Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity.”. Chem Biol. 16 (6): 644–656. DOI:10.1016/j.chembiol.2009.05.010. PMC 2844702. PMID 19549602.
↑ Jang SW, Okada M, Sayeed I, Xiao G, Stein D, Jin P, Ye K. (October 2007). „Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death.”. Proc Natl Acad Sci U S A 104 (41): 16329–16334. DOI:10.1073/pnas.0706662104. PMC 2042206. PMID 17911251.

Literatura

Indo Y (2002). „Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV. Clinical, biological and molecular aspects of mutations in TRKA(NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor.”. Clin. Auton. Res. 12 (Suppl 1): I20–32. DOI:10.1007/s102860200016. PMID 12102460.
Micera A, Lambiase A, Stampachiacchiere B, et al. (2007). „Nerve growth factor and tissue repair remodeling: trkA(NGFR) and p75(NTR), two receptors one fate.”. Cytokine Growth Factor Rev. 18 (3–4): 245–56. DOI:10.1016/j.cytogfr.2007.04.004. PMID 17531524.

Vanjske veze

GeneReviews/NCBI/NIH/UW entry on Hereditary Sensory and Autonomic Neuropathy IV

[pmid2869410-1] Martin-Zanca D, Hughes SH, Barbacid M (April 1986). „A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences”. Nature 319 (6056): 743–8. DOI:10.1038/319743a0. PMID 2869410.

[2] „Entrez Gene: NTRK1 neurotrophic tyrosine kinase, receptor, type 1”.

[pmid10708759-3] 3,0 ^3,1 ^3,2 ^3,3 Koch, A; Mancini A; Stefan M; Niedenthal R; Niemann H; Tamura T (March 2000). „Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop”. FEBS Lett. 469 (1): 72–6. DOI:10.1016/S0014-5793(00)01242-4. PMID 10708759.

[pmid10679771-4] Yano, H; Cong F; Birge R B; Goff S P; Chao M V (February 2000). „Association of the Abl tyrosine kinase with the Trk nerve growth factor receptor”. J. Neurosci. Res. 59 (3): 356–64. DOI:10.1002/(SICI)1097-4547(20000201)59:3<356::AID-JNR9>3.0.CO;2-G. PMID 10679771.

[pmid10092678-5] 5,0 ^5,1 ^5,2 Meakin, S O; MacDonald J I; Gryz E A; Kubu C J; Verdi J M (April 1999). „The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation”. J. Biol. Chem. 274 (14): 9861–70. DOI:10.1074/jbc.274.14.9861. PMID 10092678.

[pmid11733534-6] Song, Cheng; Perides George; Liu Ya Fang (February 2002). „Expression of full-length polyglutamine-expanded Huntingtin disrupts growth factor receptor signaling in rat pheochromocytoma (PC12) cells”. J. Biol. Chem. 277 (8): 6703–7. DOI:10.1074/jbc.M110338200. PMID 11733534.

[pmid10748052-7] MacDonald, J I; Gryz E A; Kubu C J; Verdi J M; Meakin S O (June 2000). „Direct binding of the signaling adapter protein Grb2 to the activation loop tyrosines on the nerve growth factor receptor tyrosine kinase, TrkA”. J. Biol. Chem. 275 (24): 18225–33. DOI:10.1074/jbc.M001862200. PMID 10748052.

[pmid10329710-8] Yamashita, H; Avraham S; Jiang S; Dikic I; Avraham H (May 1999). „The Csk homologous kinase associates with TrkA receptors and is involved in neurite outgrowth of PC12 cells”. J. Biol. Chem. 274 (21): 15059–65. DOI:10.1074/jbc.274.21.15059. PMID 10329710.

[pmid14985763-9] Nykjaer, Anders; Lee Ramee, Teng Kenneth K, Jansen Pernille, Madsen Peder, Nielsen Morten S, Jacobsen Christian, Kliemannel Marco, Schwarz Elisabeth, Willnow Thomas E, Hempstead Barbara L, Petersen Claus M (February 2004). „Sortilin is essential for proNGF-induced neuronal cell death”. Nature 427 (6977): 843–8. DOI:10.1038/nature02319. PMID 14985763.

[pmid11729324-10] Lee, R; Kermani P; Teng K K; Hempstead B L (November 2001). „Regulation of cell survival by secreted proneurotrophins”. Science 294 (5548): 1945–8. DOI:10.1126/science.1065057. PMID 11729324.

[pmid10490030-11] Wiesmann, C; Ultsch M H; Bass S H; de Vos A M (September 1999). „Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor”. Nature 401 (6749): 184–8. DOI:10.1038/43705. PMID 10490030.

[pmid1715690-12] Ohmichi, M; Decker S J; Pang L; Saltiel A R (August 1991). „Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1”. Biochem. Biophys. Res. Commun. 179 (1): 217–23. DOI:10.1016/0006-291X(91)91357-I. PMID 1715690.

[pmid9856458-13] 13,0 ^13,1 ^13,2 ^13,3 Qian, X; Riccio A; Zhang Y; Ginty D D (November 1998). „Identification and characterization of novel substrates of Trk receptors in developing neurons”. Neuron 21 (5): 1017–29. DOI:10.1016/S0896-6273(00)80620-0. PMID 9856458.

[pmid12446789-14] 14,0 ^14,1 Nakamura, Takeshi; Komiya Misako; Sone Kiyoaki; Hirose Eiji; Gotoh Noriko; Morii Hiroshi; Ohta Yasutaka; Mori Nozomu (December 2002). „Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules”. Mol. Cell. Biol. 22 (24): 8721–34. DOI:10.1128/MCB.22.24.8721-8734.2002. PMC 139861. PMID 12446789.

[pmid11244088-15] Wooten, M W; Seibenhener M L; Mamidipudi V; Diaz-Meco M T; Barker P A; Moscat J (March 2001). „The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor”. J. Biol. Chem. 276 (11): 7709–12. DOI:10.1074/jbc.C000869200. PMID 11244088.

[pmid12471037-16] Geetha T, Wooten MW (February 2003). „Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling”. J. Biol. Chem. 278 (7): 4730–9. DOI:10.1074/jbc.M208468200. PMID 12471037.

[pmid18457658-17] Jadhav T, Geetha T, Jiang J, Wooten MW (July 2008). „Identification of a consensus site for TRAF6/p62 polyubiquitination”. Biochem. Biophys. Res. Commun. 371 (3): 521–4. DOI:10.1016/j.bbrc.2008.04.138. PMC 2474794. PMID 18457658.

[pmid18174161-18] Wooten MW, Geetha T, Babu JR, Seibenhener ML, Peng J, Cox N, Diaz-Meco MT, Moscat J (March 2008). „Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins”. J. Biol. Chem. 283 (11): 6783–9. DOI:10.1074/jbc.M709496200. PMID 18174161.

[pmid8183561-19] Borrello, M G; Pelicci G; Arighi E; De Filippis L; Greco A; Bongarzone I; Rizzetti M; Pelicci P G i dr.. (June 1994). „The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins”. Oncogene 9 (6): 1661–8. PMID 8183561.

[pmid19549602-20] Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K. (June 2009). „Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity.”. Chem Biol. 16 (6): 644–656. DOI:10.1016/j.chembiol.2009.05.010. PMC 2844702. PMID 19549602.

[pmid17911251-21] Jang SW, Okada M, Sayeed I, Xiao G, Stein D, Jin P, Ye K. (October 2007). „Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death.”. Proc Natl Acad Sci U S A 104 (41): 16329–16334. DOI:10.1073/pnas.0706662104. PMC 2042206. PMID 17911251.

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p r u Receptori: Receptori faktora rasta
Nervni faktori rasta	niski afinitet/p75 - visok afinitet Trk (TrkA, TrkB, TrkC) - Cilijarni neurotrofni faktor
Somatomedin	Insulinu-sličan faktor rasta 1 - Insulinu-sličan faktor rasta 2
CSF	Stem ćelijski faktor - Eritropoietin
TGF put	TGF-beta (1, 2) - Aktivin (1, 2) - Bone morfogenetski protein (1, 2)
Drugi	Hepatocitni faktor rasta - ErbB/Epidermalni faktor rasta - Fibroblast faktor rasta (1, 2, 3, 4) - Trombocit-izvedeni faktor rasta (A, B) - VEGF (1, 2, 3)
vidi isto Faktori rasta
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)