TNK2

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Tirozinska kinaza, nereceptor, 2

PDB prikaz baziran na 1cf4.
Dostupne strukture
1CF4, 1U46, 1U4D, 1U54, 3EQP, 3EQR, 4EWH, 4HZR, 4HZS, 4ID7
Identifikatori
SimboliTNK2; ACK; ACK-1; ACK1; p21cdc42Hs
Vanjski IDOMIM606994 MGI1858308 HomoloGene4224 GeneCards: TNK2 Gene
EC broj2.7.11.1 2.7.10.2, 2.7.11.1
Pregled RNK izražavanja
PBB GE TNK2 203838 s at tn.png
PBB GE TNK2 203839 s at tn.png
podaci
Ortolozi
VrstaČovekMiš
Entrez1018851789
EnsemblENSG00000061938ENSMUSG00000022791
UniProtQ07912O54967
Ref. Sekv. (iRNK)NM_001010938NM_001110147
Ref. Sekv. (protein)NP_001010938NP_001103617
Lokacija (UCSC)Chr 3:
195.59 - 195.64 Mb
Chr 16:
32.64 - 32.68 Mb
PubMed pretraga[1][2]

Aktivirana CDC42 kinaza 1, takođe poznata kao ACK1, je enzim koji je kod ljudi kodiran TNK2 genom.[1][2][3][4][5]

TNK2 gen kodira nereceptorsku tirozinsku kinazu, ACK1, koja se vezuje za višestruke receptorske tirozinske kinaze e.g. EGFR, MERTK, AXL, HER2 i insulinski receptor (IR). ACK1 takođe interaguje sa Cdc42Hs u njegovoj GTP-vezanoj formi i inhibira intrinzičnu i GTPaznu aktivnost Cdc42H. Vezivanje je posredovano jedistvenom sekvencom od 47 aminokiselina između C-terminusa i SH3 domena. Ovaj protein učestvuje u regulatornom mehanizmu kojim se održava GTP-vezana aktivna forma Cdc42H i koji je direktno povezan sa torozinsko fosforilacionim putem prenosa signala. Poznato je nekoliko alternativno splajsovanih transkriptnih varijanti ovog gena, ali se izražavaju samo dve varijante.[5]

Interakcije[uredi - уреди | uredi izvor]

ACK1 ili TNK2 formira interakcije sa AKT,[3] Androgenskim receptorom ili AR,[6] tumornim supresorom WWOX,[7] FYN[8] i Grb2.[9][10] ACK1 interakcije sa njegovim supstratima dovode do njihove fosforilacije na specifičnim tirozinskim ostacima. ACK1 direktno fosforiliše AKT na tirozinu 176, AR na tirosizinima 267 i 363, i WWOX na torozinu 287. Ack1-AR signalizacije takođe učestvuje u regulaciji ATM nivoaa[11]

Reference[uredi - уреди | uredi izvor]

  1. Mahajan K, Mahajan NP (August 2010). "Shepherding AKT and androgen receptor by Ack1 tyrosine kinase.". J Cell Physiol. 224 (2): 327–23. PMID 20432460. doi:10.1002/jcp.22162. 
  2. Manser E, Leung T, Salihuddin H, Tan L, Lim L (June 1993). "A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42". Nature 363 (6427): 364–7. PMID 8497321. doi:10.1038/363364a0. 
  3. 3,0 3,1 Mahajan K, Coppola D, Challa S, Fang B, Chen YA, Zhu W, Lopez AS, Koomen J, Engelman RW, Rivera C, Muraoka-Cook RS, Cheng JQ, Schönbrunn E, Sebti SM, Earp HS, Mahajan NP. (March 2010). "Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation". PLoS ONE 5 (3): e9646. PMID 20333297. doi:10.1371/journal.pone.0009646. 
  4. Yokoyama N, Miller WT (November 2003). "Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck". J Biol Chem 278 (48): 47713–23. PMID 14506255. doi:10.1074/jbc.M306716200. 
  5. 5,0 5,1 "Entrez Gene: TNK2 tyrosine kinase, non-receptor, 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10188. 
  6. Mahajan NP, Liu Y, Majumder S, Warren MR, Parker CE, Mohler JL, Earp HS, Whang YE. (May 2007). "Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation.". Proc Natl Acad Sci U S A. 104 (20): 8438–43. PMID 17494760. doi:10.1073/pnas.0700420104. 
  7. Mahajan NP, Whang YE, Mohler JL, Earp HS. (November 2005). "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox.". Cancer Res. 65 (22): 10514–23. PMID 16288044. doi:10.1158/0008-5472.can-05-1127. 
  8. Linseman DA, Heidenreich KA, Fisher SK (February 2001). "Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway". J. Biol. Chem. 276 (8): 5622–8. PMID 11087735. doi:10.1074/jbc.M006812200. 
  9. Satoh T, Kato J, Nishida K, Kaziro Y (May 1996). "Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation". FEBS Lett. 386 (2-3): 230–4. PMID 8647288. doi:10.1016/0014-5793(96)00449-8. 
  10. Kato-Stankiewicz J, Ueda S, Kataoka T, Kaziro Y, Satoh T (June 2001). "Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner". Biochem. Biophys. Res. Commun. 284 (2): 470–7. PMID 11394904. doi:10.1006/bbrc.2001.5004. 
  11. Mahajan K, Coppola D, Rawal B, Chen YA, Lawrence HR, Engelman RW, Lawrence NJ, Mahajan NP. (June 2012). "Ack1-mediated androgen receptor phosphorylation modulates radiation resistance in castration-resistant prostate cancer.". J Biol Chem. 287 (26): 22112–22. PMID 22566699. doi:10.1074/jbc.M112.357384. 

Literatura[uredi - уреди | uredi izvor]

  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8. 
  • Satoh T, Kato J, Nishida K, Kaziro Y (1996). "Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation". FEBS Lett. 386 (2–3): 230–4. PMID 8647288. doi:10.1016/0014-5793(96)00449-8. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3. 
  • Mott HR, Owen D, Nietlispach D et al. (1999). "Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK". Nature 399 (6734): 384–8. PMID 10360579. doi:10.1038/20732. 
  • Eisenmann KM, McCarthy JB, Simpson MA et al. (2000). "Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas". Nat. Cell Biol. 1 (8): 507–13. PMID 10587647. doi:10.1038/70302. 
  • Kato J, Kaziro Y, Satoh T (2000). "Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation". Biochem. Biophys. Res. Commun. 268 (1): 141–7. PMID 10652228. doi:10.1006/bbrc.2000.2106. 
  • Owen D, Mott HR, Laue ED, Lowe PN (2000). "Residues in Cdc42 that specify binding to individual CRIB effector proteins". Biochemistry 39 (6): 1243–50. PMID 10684602. doi:10.1021/bi991567z. 
  • Kiyono M, Kato J, Kataoka T et al. (2000). "Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1". J. Biol. Chem. 275 (38): 29788–93. PMID 10882715. doi:10.1074/jbc.M001378200. 
  • Linseman DA, Heidenreich KA, Fisher SK (2001). "Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway". J. Biol. Chem. 276 (8): 5622–8. PMID 11087735. doi:10.1074/jbc.M006812200. 
  • Teo M, Tan L, Lim L, Manser E (2001). "The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors". J. Biol. Chem. 276 (21): 18392–8. PMID 11278436. doi:10.1074/jbc.M008795200. 
  • Kato-Stankiewicz J, Ueda S, Kataoka T et al. (2001). "Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner". Biochem. Biophys. Res. Commun. 284 (2): 470–7. PMID 11394904. doi:10.1006/bbrc.2001.5004. 
  • Oda T, Muramatsu MA, Isogai T et al. (2001). "HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells". Biochem. Biophys. Res. Commun. 288 (5): 1078–86. PMID 11700021. doi:10.1006/bbrc.2001.5890. 
  • Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMC 139241. PMID 12477932. doi:10.1073/pnas.242603899. 
  • Salomon AR, Ficarro SB, Brill LM et al. (2003). "Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry". Proc. Natl. Acad. Sci. U.S.A. 100 (2): 443–8. PMC 141014. PMID 12522270. doi:10.1073/pnas.2436191100. 
  • Ahmed I, Calle Y, Sayed MA et al. (2004). "Cdc42-dependent nuclear translocation of non-receptor tyrosine kinase, ACK". Biochem. Biophys. Res. Commun. 314 (2): 571–9. PMID 14733946. doi:10.1016/j.bbrc.2003.12.137. 
  • Gu Y, Lin Q, Childress C, Yang W (2004). "Identification of the region in Cdc42 that confers the binding specificity to activated Cdc42-associated kinase". J. Biol. Chem. 279 (29): 30507–13. PMID 15123659. doi:10.1074/jbc.M313518200. 
  • Brandenberger R, Wei H, Zhang S et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. PMID 15146197. doi:10.1038/nbt971. 
  • Lougheed JC, Chen RH, Mak P, Stout TJ (2004). "Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1". J. Biol. Chem. 279 (42): 44039–45. PMID 15308621. doi:10.1074/jbc.M406703200. 

Vanjske veze[uredi - уреди | uredi izvor]

  • TNK2 human gene location in the UCSC Genome Browser.
  • TNK2 human gene details in the UCSC Genome Browser.