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Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics

  • Authors:
    • Masaya Miyazaki
    • Masaki Hiramoto
    • Naoharu Takano
    • Hiroko Kokuba
    • Jun Takemura
    • Mayumi Tokuhisa
    • Hirotsugu Hino
    • Hiromi Kazama
    • Keisuke Miyazawa
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Tokyo Medical University, Tokyo 160‑8402, Japan, Laboratory of Electron Microscopy, Tokyo Medical University, Tokyo 160‑8402, Japan
    Copyright: © Miyazaki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 195
    |
    Published online on: August 30, 2021
       https://doi.org/10.3892/ijmm.2021.5028
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Abstract

The autophagy‑lysosome system allows cells to adapt to environmental changes by regulating the degradation and recycling of cellular components, and to maintain homeostasis by removing aggregated proteins and defective organelles. Cyclin G‑associated kinase (GAK) is involved in the regulation of clathrin‑dependent endocytosis and cell cycle progression. In addition, a single nucleotide polymorphism at the GAK locus has been reported as a risk factor for Parkinson's disease. However, the roles of GAK in the autophagy‑lysosome system are not completely understood, thus the present study aimed to clarify this. In the present study, under genetic disruption or chemical inhibition of GAK, analyzing autophagic flux and observing morphological changes of autophagosomes and autolysosomes revealed that GAK controlled lysosomal dynamics via actomyosin regulation, resulting in a steady progression of autophagy. GAK knockout (KO) in A549 cells impaired autophagosome‑lysosome fusion and autophagic lysosome reformation, which resulted in the accumulation of enlarged autophagosomes and autolysosomes during prolonged starvation. The stagnation of autophagic flux accompanied by these phenomena was also observed with the addition of a GAK inhibitor. Furthermore, the addition of Rho‑associated protein kinase (ROCK) inhibitor or ROCK1 knockdown mitigated GAK KO‑mediated effects. The results suggested a vital role of GAK in controlling lysosomal dynamics via maintaining lysosomal homeostasis during autophagy.
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View References

1 

Morishita H and Mizushima N: Diverse cellular roles of autophagy. Annu Rev Cell Dev Biol. 35:453–475. 2019. View Article : Google Scholar : PubMed/NCBI

2 

King KE, Losier TT and Russell RC: Regulation of autophagy enzymes by nutrient signaling. Trends Biochem Sci. 46:687–700. 2021. View Article : Google Scholar : PubMed/NCBI

3 

Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H and Mizushima N: Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 441:885–889. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Alers S, Löffler AS, Wesselborg S and Stork B: Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: Cross talk, shortcuts, and feedbacks. Mol Cell Biol. 32:2–11. 2012. View Article : Google Scholar :

5 

Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, Choi AM, Chu CT, Codogno P, Colombo MI, et al: Molecular definitions of autophagy and related processes. EMBO J. 36:1811–1836. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Mercer TJ, Gubas A and Tooze SA: A molecular perspective of mammalian autophagosome biogenesis. J Biol Chem. 293:5386–5395. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Nishimura T and Tooze SA: Emerging roles of ATG proteins and membrane lipids in autophagosome formation. Cell Discov. 6:322020. View Article : Google Scholar : PubMed/NCBI

8 

Parzych KR and Klionsky DJ: Vacuolar hydrolysis and efflux: Current knowledge and unanswered questions. Autophagy. 15:212–227. 2019. View Article : Google Scholar :

9 

Yim WW and Mizushima N: Lysosome biology in autophagy. Cell Discov. 6:62020. View Article : Google Scholar : PubMed/NCBI

10 

Kawabata T and Yoshimori T: Autophagosome biogenesis and human health. Cell Discov. 6:332020. View Article : Google Scholar : PubMed/NCBI

11 

Mizushima N and Levine B: Autophagy in human diseases. N Engl J Med. 383:1564–1576. 2020. View Article : Google Scholar : PubMed/NCBI

12 

Ballabio A and Bonifacino JS: Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 21:101–118. 2020. View Article : Google Scholar

13 

Pu J, Guardia CM, Keren-Kaplan T and Bonifacino JS: Mechanisms and functions of lysosome positioning. J Cell Sci. 129:4329–4339. 2016.PubMed/NCBI

14 

de Araujo ME, Liebscher G, Hess MW and Huber LA: Lysosomal size matters. Traffic. 21:60–75. 2020. View Article : Google Scholar :

15 

Chen Y and Yu L: Recent progress in autophagic lysosome reformation. Traffic. 18:358–361. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Korolchuk VI, Saiki S, Lichtenberg M, Siddiqi FH, Roberts EA, Imarisio S, Jahreiss L, Sarkar S, Futter M, Menzies FM, et al: Lysosomal positioning coordinates cellular nutrient responses. Nat Cell Biol. 13:453–460. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Dalle Pezze P, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van Eunen K, Tölle RC, Schwarz JJ, et al: A systems study reveals concurrent activation of AMPK and mTOR by amino acids. Nat Commun. 7:132542016. View Article : Google Scholar : PubMed/NCBI

18 

Liu GY and Sabatini DM: mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 21:183–203. 2020. View Article : Google Scholar : PubMed/NCBI

19 

Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, et al: Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 465:942–946. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Kruppa AJ, Kendrick-Jones J and Buss F: Myosins, actin and autophagy. Traffic. 17:878–890. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Kast DJ and Dominguez R: The cytoskeleton-autophagy connection. Curr Biol. 27:R318–R326. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Greener T, Zhao X, Nojima H, Eisenberg E and Greene LE: Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells. J Biol Chem. 275:1365–1370. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Lee DW, Wu X, Eisenberg E and Greene LE: Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. J Cell Sci. 119:3502–3512. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Kanaoka Y, Kimura SH, Okazaki I, Ikeda M and Nojima H: GAK: A cyclin G associated kinase contains a tensin/auxilin-like domain. FEBS Lett. 402:73–80. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Shimizu H, Nagamori I, Yabuta N and Nojima H: GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression. J Cell Sci. 122:3145–3152. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Naito Y, Shimizu H, Kasama T, Sato J, Tabara H, Okamoto A, Yabuta N and Nojima H: Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B'γ subunit. Cell Cycle. 11:604–616. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Fukushima K, Wang M, Naito Y, Uchihashi T, Kato Y, Mukai S, Yabuta N and Nojima H: GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase. Cell Cycle. 16:415–427. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Yabuno Y, Uchihashi T, Sasakura T, Shimizu H, Naito Y, Fukushima K, Ota K, Kogo M, Nojima H and Yabuta N: Clathrin heavy chain phosphorylated at T606 plays a role in proper cell division. Cell Cycle. 18:1976–1994. 2019. View Article : Google Scholar : PubMed/NCBI

29 

Zhao X, Greener T, Al-Hasani H, Cushman SW, Eisenberg E and Greene LE: Expression of auxilin or AP180 inhibits endocytosis by mislocalizing clathrin: Evidence for formation of nascent pits containing AP1 or AP2 but not clathrin. J Cell Sci. 114:353–365. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Lee DW, Zhao X, Zhang F, Eisenberg E and Greene LE: Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors. J Cell Sci. 118:4311–4321. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Zhang CX, Engqvist-Goldstein AE, Carreno S, Owen DJ, Smythe E and Drubin DG: Multiple roles for cyclin G-associated kinase in clathrin-mediated sorting events. Traffic. 6:1103–1113. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Zhang L, Gjoerup O and Roberts TM: The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling. Proc Natl Acad Sci USA. 101:10296–10301. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Kametaka S, Moriyama K, Burgos PV, Eisenberg E, Greene LE, Mattera R and Bonifacino JS: Canonical interaction of cyclin G associated kinase with adaptor protein 1 regulates lysosomal enzyme sorting. Mol Biol Cell. 18:2991–3001. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK, Kalia LV, Lobbestael E, Chia R, Ndukwe K, et al: Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci USA. 111:2626–2631. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Plowey ED, Cherra SJ III, Liu YJ and Chu CT: Role of autophagy in G2019S-LRRK2 -associated neurite shortening in differentiated SH-SY5Y cells. J Neurochem. 105:1048–1056. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Gómez-Suaga P, Luzón-Toro B, Churamani D, Zhang L, Bloor-Young D, Patel S, Woodman PG, Churchill GC and Hilfiker S: Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Hum Mol Genet. 21:511–525. 2012. View Article : Google Scholar :

37 

Madureira M, Connor-Robson N and Wade-Martins R: LRRK2: Autophagy and lysosomal activity. Front Neurosci. 14:4982020. View Article : Google Scholar

38 

Susa M, Choy E, Liu X, Schwab J, Hornicek FJ, Mankin H and Duan Z: Cyclin G-associated kinase is necessary for osteosarcoma cell proliferation and receptor trafficking. Mol Cancer Ther. 9:3342–3350. 2010. View Article : Google Scholar : PubMed/NCBI

39 

Rhodes SL, Sinsheimer JS, Bordelon Y, Bronstein JM and Ritz B: Replication of GWAS associations for GAK and MAPT in Parkinson's disease. Ann Hum Genet. 75:195–200. 2011.

40 

Dumitriu A, Pacheco CD, Wilk JB, Strathearn KE, Latourelle JC, Goldwurm S, Pezzoli G, Rochet JC, Lindquist S and Myers RH: Cyclin-G-associated kinase modifies α-synuclein expression levels and toxicity in Parkinson's disease: Results from the GenePD Study. Hum Mol Genet. 20:1478–1487. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Ma ZG, He F and Xu J: Quantitative assessment of the association between GAK rs1564282 C/T polymorphism and the risk of Parkinson's disease. J Clin Neurosci. 22:1077–1080. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA and Zhang F: Multiplex genome engineering using CRISPR/Cas systems. Science. 339:819–823. 2013. View Article : Google Scholar : PubMed/NCBI

43 

Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA and Zhang F: Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 8:2281–2308. 2013. View Article : Google Scholar : PubMed/NCBI

44 

Tanaka H, Hino H, Moriya S, Kazama H, Miyazaki M, Takano N, Hiramoto M, Tsukahara K and Miyazawa K: Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin. Biochem Biophys Rep. 22:1007502020.PubMed/NCBI

45 

Kaizuka T, Morishita H, Hama Y, Tsukamoto S, Matsui T, Toyota Y, Kodama A, Ishihara T, Mizushima T and Mizushima N: An autophagic flux probe that releases an internal control. Mol Cell. 64:835–849. 2016. View Article : Google Scholar : PubMed/NCBI

46 

Spangle JM, Ghosh-Choudhury N and Munger K: Activation of cap-dependent translation by mucosal human papillomavirus E6 proteins is dependent on the integrity of the LXXLL binding motif. J Virol. 86:7466–7472. 2012. View Article : Google Scholar : PubMed/NCBI

47 

Stewart SA, Dykxhoorn DM, Palliser D, Mizuno H, Yu EY, An DS, Sabatini DM, Chen IS, Hahn WC, Sharp PA, et al: Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA. 9:493–501. 2003. View Article : Google Scholar : PubMed/NCBI

48 

Yokota A, Hiramoto M, Hino H, Tokuhisa M, Miyazaki M, Kazama H, Takano N and Miyazawa K: Sequestosome 1 (p62) accumulation in breast cancer cells suppresses progesterone receptor expression via argonaute 2. Biochem Biophys Res Commun. 531:256–263. 2020. View Article : Google Scholar : PubMed/NCBI

49 

Lamb CA, Joachim J and Tooze SA: Quantifying autophagic structures in mammalian cells using confocal microscopy. Methods Enzymol. 587:21–42. 2017. View Article : Google Scholar : PubMed/NCBI

50 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

51 

Poole B and Ohkuma S: Effect of weak bases on the intralysosomal pH in mouse peritoneal macrophages. J Cell Biol. 90:665–669. 1981. View Article : Google Scholar : PubMed/NCBI

52 

Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A and Thompson CB: Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest. 117:326–336. 2007. View Article : Google Scholar : PubMed/NCBI

53 

Maclean KH, Dorsey FC, Cleveland JL and Kastan MB: Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. J Clin Invest. 118:79–88. 2008. View Article : Google Scholar

54 

Rong Y, Liu M, Ma L, Du W, Zhang H, Tian Y, Cao Z, Li Y, Ren H, Zhang C, et al: Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. Nat Cell Biol. 14:924–934. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Chang J, Lee S and Blackstone C: Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. J Clin Invest. 124:5249–5262. 2014. View Article : Google Scholar : PubMed/NCBI

56 

McGrath MJ, Eramo MJ, Gurung R, Sriratana A, Gehrig SM, Lynch GS, Lourdes SR, Koentgen F, Feeney SJ, Lazarou M, et al: Defective lysosome reformation during autophagy causes skeletal muscle disease. J Clin Invest. 131:e1351242021. View Article : Google Scholar :

57 

Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M and Narumiya S: Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 389:990–994. 1997. View Article : Google Scholar : PubMed/NCBI

58 

Julian L and Olson MF: Rho-associated coiled-coil containing kinases (ROCK): Structure, regulation, and functions. Small GTPases. 5:e298462014. View Article : Google Scholar : PubMed/NCBI

59 

Kast DJ, Zajac AL, Holzbaur EL, Ostap EM and Dominguez R: WHAMM Directs the Arp2/3 Complex to the ER for autophagosome biogenesis through an Actin comet tail mechanism. Curr Biol. 25:1791–1797. 2015. View Article : Google Scholar : PubMed/NCBI

60 

Mathiowetz AJ, Baple E, Russo AJ, Coulter AM, Carrano E, Brown JD, Jinks RN, Crosby AH and Campellone KG: An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway. Mol Biol Cell. 28:2492–2507. 2017. View Article : Google Scholar : PubMed/NCBI

61 

Dai A, Yu L and Wang HW: WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes. Nat Commun. 10:36992019. View Article : Google Scholar : PubMed/NCBI

62 

Nakamura S, Hasegawa J and Yoshimori T: Regulation of lysosomal phosphoinositide balance by INPP5E is essential for autophagosome-lysosome fusion. Autophagy. 12:2500–2501. 2016. View Article : Google Scholar : PubMed/NCBI

63 

Nakamura S and Yoshimori T: New insights into autophagosome-lysosome fusion. J Cell Sci. 130:1209–1216. 2017.PubMed/NCBI

64 

Henry KR, D'Hondt K, Chang JS, Nix DA, Cope MJ, Chan CS, Drubin DG and Lemmon SK: The actin-regulating kinase Prk1p negatively regulates Scd5p, a suppressor of clathrin deficiency, in actin organization and endocytosis. Curr Biol. 13:1564–1569. 2003. View Article : Google Scholar : PubMed/NCBI

65 

Sekiya-Kawasaki M, Groen AC, Cope MJ, Kaksonen M, Watson HA, Zhang C, Shokat KM, Wendland B, McDonald KL, McCaffery JM and Drubin DG: Dynamic phosphoregulation of the cortical actin cytoskeleton and endocytic machinery revealed by real-time chemical genetic analysis. J Cell Biol. 162:765–772. 2003. View Article : Google Scholar : PubMed/NCBI

66 

Toshima J, Toshima JY, Martin AC and Drubin DG: Phosphoregulation of Arp2/3-dependent actin assembly during receptor-mediated endocytosis. Nat Cell Biol. 7:246–254. 2005. View Article : Google Scholar : PubMed/NCBI

67 

Paisán-Ruíz C, Jain S, Evans EW, Gilks WP, Simón J, van der Brug M, López de Munain A, Aparicio S, Gil AM, Khan N, et al: Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron. 44:595–600. 2004. View Article : Google Scholar : PubMed/NCBI

68 

Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, et al: Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 44:601–607. 2004. View Article : Google Scholar : PubMed/NCBI

69 

Zimprich A, Müller-Myhsok B, Farrer M, Leitner P, Sharma M, Hulihan M, Lockhart P, Strongosky A, Kachergus J, Calne DB, et al: The PARK8 locus in autosomal dominant parkinsonism: Confirmation of linkage and further delineation of the disease-containing interval. Am J Hum Genet. 74:11–19. 2004. View Article : Google Scholar

70 

Usmani A, Shavarebi F and Hiniker A: The Cell Biology of LRRK2 in Parkinson's disease. Mol Cell Biol. 41:e00660–20. 2021. View Article : Google Scholar : PubMed/NCBI

71 

Clark EH, Vázquez de la Torre A, Hoshikawa T and Briston T: Targeting mitophagy in Parkinson's disease. J Biol Chem. 296:1002092020. View Article : Google Scholar : PubMed/NCBI

72 

Malpartida AB, Williamson M, Narendra DP, Wade-Martins R and Ryan BJ: Mitochondrial dysfunction and mitophagy in Parkinson's disease: From mechanism to therapy. Trends Biochem Sci. 46:329–343. 2020. View Article : Google Scholar : PubMed/NCBI

73 

Plotegher N and Duchen MR: Crosstalk between Lysosomes and Mitochondria in Parkinson's disease. Front Cell Dev Biol. 5:1102017. View Article : Google Scholar

74 

Nguyen M, Wong YC, Ysselstein D, Severino A and Krainc D: Synaptic, Mitochondrial, and Lysosomal dysfunction in Parkinson's disease. Trends Neurosci. 42:140–149. 2019. View Article : Google Scholar

75 

Vidyadhara DJ, Lee JE and Chandra SS: Role of the endolysosomal system in Parkinson's disease. J Neurochem. 150:487–506. 2019. View Article : Google Scholar : PubMed/NCBI

76 

Oxnard GR, Janjigian YY, Arcila ME, Sima CS, Kass SL, Riely GJ, Pao W, Kris MG, Ladanyi M, Azzoli CG and Miller VA: Maintained sensitivity to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer recurring after adjuvant erlotinib or gefitinib. Clin Cancer Res. 17:6322–6328. 2011. View Article : Google Scholar : PubMed/NCBI

77 

Han W, Pan H, Chen Y, Sun J, Wang Y, Li J, Ge W, Feng L, Lin X, Wang X, et al: EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells. PLoS One. 6:e186912011. View Article : Google Scholar : PubMed/NCBI

78 

Sugita S, Ito K, Yamashiro Y, Moriya S, Che XF, Yokoyama T, Hiramoto M and Miyazawa K: EGFR-independent autophagy induction with gefitinib and enhancement of its cytotoxic effect by targeting autophagy with clarithromycin in non-small cell lung cancer cells. Biochem Biophys Res Commun. 461:28–34. 2015. View Article : Google Scholar : PubMed/NCBI

79 

Brehmer D, Greff Z, Godl K, Blencke S, Kurtenbach A, Weber M, Müller S, Klebl B, Cotton M, Kéri G, et al: Cellular targets of gefitinib. Cancer Res. 65:379–382. 2005.PubMed/NCBI

80 

Yamamoto N, Honma M and Suzuki H: Off-target serine/threonine kinase 10 inhibition by erlotinib enhances lymphocytic activity leading to severe skin disorders. Mol Pharmacol. 80:466–475. 2011. View Article : Google Scholar : PubMed/NCBI

81 

Ray MR, Wafa LA, Cheng H, Snoek R, Fazli L, Gleave M and Rennie PS: Cyclin G-associated kinase: A novel androgen receptor-interacting transcriptional coactivator that is overexpressed in hormone refractory prostate cancer. Int J Cancer. 118:1108–1119. 2006. View Article : Google Scholar

82 

Sooro MA, Zhang N and Zhang P: Targeting EGFR-mediated autophagy as a potential strategy for cancer therapy. Int J Cancer. 143:2116–2125. 2018. View Article : Google Scholar : PubMed/NCBI

83 

Wu M and Zhang P: EGFR-mediated autophagy in tumourigenesis and therapeutic resistance. Cancer Lett. 469:207–216. 2020. View Article : Google Scholar

84 

Rehman SK, Haynes J, Collignon E, Brown KR, Wang Y, Nixon AM, Bruce JP, Wintersinger JA, Singh Mer A, Lo EB, et al: Colorectal cancer cells enter a Diapause-like DTP state to survive chemotherapy. Cell. 184:226–242.e221. 2021. View Article : Google Scholar : PubMed/NCBI

85 

Nagle MW, Latourelle JC, Labadorf A, Dumitriu A, Hadzi TC, Beach TG and Myers RH: The 4p163 Parkinson disease risk locus is associated with GAK expression and genes involved with the synaptic vesicle membrane. PLoS One. 11:e01609252016. View Article : Google Scholar

86 

Tumbarello DA, Kendrick-Jones J and Buss F: Myosin VI and its cargo adaptors-linking endocytosis and autophagy. J Cell Sci. 126:2561–2570. 2013.PubMed/NCBI

87 

Bilanges B, Posor Y and Vanhaesebroeck B: PI3K isoforms in cell signalling and vesicle trafficking. Nat Rev Mol Cell Biol. 20:515–534. 2019. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Miyazaki M, Hiramoto M, Takano N, Kokuba H, Takemura J, Tokuhisa M, Hino H, Kazama H and Miyazawa K: Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics. Int J Mol Med 48: 195, 2021.
APA
Miyazaki, M., Hiramoto, M., Takano, N., Kokuba, H., Takemura, J., Tokuhisa, M. ... Miyazawa, K. (2021). Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics. International Journal of Molecular Medicine, 48, 195. https://doi.org/10.3892/ijmm.2021.5028
MLA
Miyazaki, M., Hiramoto, M., Takano, N., Kokuba, H., Takemura, J., Tokuhisa, M., Hino, H., Kazama, H., Miyazawa, K."Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics". International Journal of Molecular Medicine 48.4 (2021): 195.
Chicago
Miyazaki, M., Hiramoto, M., Takano, N., Kokuba, H., Takemura, J., Tokuhisa, M., Hino, H., Kazama, H., Miyazawa, K."Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics". International Journal of Molecular Medicine 48, no. 4 (2021): 195. https://doi.org/10.3892/ijmm.2021.5028
Copy and paste a formatted citation
x
Spandidos Publications style
Miyazaki M, Hiramoto M, Takano N, Kokuba H, Takemura J, Tokuhisa M, Hino H, Kazama H and Miyazawa K: Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics. Int J Mol Med 48: 195, 2021.
APA
Miyazaki, M., Hiramoto, M., Takano, N., Kokuba, H., Takemura, J., Tokuhisa, M. ... Miyazawa, K. (2021). Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics. International Journal of Molecular Medicine, 48, 195. https://doi.org/10.3892/ijmm.2021.5028
MLA
Miyazaki, M., Hiramoto, M., Takano, N., Kokuba, H., Takemura, J., Tokuhisa, M., Hino, H., Kazama, H., Miyazawa, K."Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics". International Journal of Molecular Medicine 48.4 (2021): 195.
Chicago
Miyazaki, M., Hiramoto, M., Takano, N., Kokuba, H., Takemura, J., Tokuhisa, M., Hino, H., Kazama, H., Miyazawa, K."Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics". International Journal of Molecular Medicine 48, no. 4 (2021): 195. https://doi.org/10.3892/ijmm.2021.5028
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