請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/21109完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李芳仁 | |
| dc.contributor.author | Kuan-Jung Chen | en |
| dc.contributor.author | 陳冠融 | zh_TW |
| dc.date.accessioned | 2021-06-08T03:27:07Z | - |
| dc.date.copyright | 2020-03-12 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-01-10 | |
| dc.identifier.citation | 1. D'Souza-Schorey, C. and P. Chavrier, ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol, 2006. 7(5): p. 347-58.
2. Gillingham, A.K. and S. Munro, The small G proteins of the Arf family and their regulators. Annu Rev Cell Dev Biol, 2007. 23: p. 579-611. 3. Lin, C.Y., et al., ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli. J Biol Chem, 2000. 275(48): p. 37815-23. 4. Lin, C.Y., et al., A developmentally regulated ARF-like 5 protein (ARL5), localized to nuclei and nucleoli, interacts with heterochromatin protein 1. J Cell Sci, 2002. 115(Pt 23): p. 4433-45. 5. Schurmann, A., et al., Reduced sperm count and normal fertility in male mice with targeted disruption of the ADP-ribosylation factor-like 4 (Arl4) gene. Mol Cell Biol, 2002. 22(8): p. 2761-8. 6. Wei, S.M., et al., ADP-ribosylation factor like 7 (ARL7) interacts with alpha-tubulin and modulates intracellular vesicular transport. Biochem Biophys Res Commun, 2009. 384(3): p. 352-6. 7. Engel, T., et al., ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export. FEBS Lett, 2004. 566(1-3): p. 241-6. 8. Lin, Y.C., et al., ARL4A acts with GCC185 to modulate Golgi complex organization. J Cell Sci, 2011. 124(Pt 23): p. 4014-26. 9. Li, C.C., et al., GTP-binding-defective ARL4D alters mitochondrial morphology and membrane potential. PLoS One, 2012. 7(8): p. e43552. 10. Chiang, T.S., H.F. Wu, and F.S. Lee, ADP-ribosylation factor-like 4C binding to filamin-A modulates filopodium formation and cell migration. Mol Biol Cell, 2017. 28(22): p. 3013-3028. 11. Donaldson, J.G. and C.L. Jackson, ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol, 2011. 12(6): p. 362-75. 12. Chiang, T.S., et al., ADP-ribosylation factor-like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation. Mol Biol Cell, 2019. 30(1): p. 69-81. 13. Parsons, J.T., A.R. Horwitz, and M.A. Schwartz, Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol, 2010. 11(9): p. 633-43. 14. Balkovetz, D.F., et al., Gene expression alterations during HGF-induced dedifferentiation of a renal tubular epithelial cell line (MDCK) using a novel canine DNA microarray. Am J Physiol Renal Physiol, 2004. 286(4): p. F702-10. 15. Kubosaki, A., et al., Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation. Genome Biol, 2009. 10(4): p. R41. 16. Delorme-Walker, V.D., et al., Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration. J Cell Biol, 2011. 193(7): p. 1289-303. 17. Zhao, Z.S. and E. Manser, PAK family kinases: Physiological roles and regulation. Cell Logist, 2012. 2(2): p. 59-68. 18. Ma, Q.L., et al., PAK in Alzheimer disease, Huntington disease and X-linked mental retardation. Cell Logist, 2012. 2(2): p. 117-125. 19. Semenova, G. and J. Chernoff, Targeting PAK1. Biochem Soc Trans, 2017. 45(1): p. 79-88. 20. Bokoch, G.M., Biology of the p21-activated kinases. Annu Rev Biochem, 2003. 72: p. 743-81. 21. Daniels, R.H., F.T. Zenke, and G.M. Bokoch, alphaPix stimulates p21-activated kinase activity through exchange factor-dependent and -independent mechanisms. J Biol Chem, 1999. 274(10): p. 6047-50. 22. Loo, T.H., et al., GIT1 activates p21-activated kinase through a mechanism independent of p21 binding. Mol Cell Biol, 2004. 24(9): p. 3849-59. 23. Lu, W., et al., Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck. Curr Biol, 1997. 7(2): p. 85-94. 24. del Pozo, M.A., et al., Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. EMBO J, 2000. 19(9): p. 2008-14. 25. Bokoch, G.M., et al., Interaction of the Nck adapter protein with p21-activated kinase (PAK1). J Biol Chem, 1996. 271(42): p. 25746-9. 26. Daniels, R.H., P.S. Hall, and G.M. Bokoch, Membrane targeting of p21-activated kinase 1 (PAK1) induces neurite outgrowth from PC12 cells. EMBO J, 1998. 17(3): p. 754-64. 27. King, C.C., et al., Sphingosine is a novel activator of 3-phosphoinositide-dependent kinase 1. J Biol Chem, 2000. 275(24): p. 18108-13. 28. Bokoch, G.M., et al., A GTPase-independent mechanism of p21-activated kinase activation. Regulation by sphingosine and other biologically active lipids. J Biol Chem, 1998. 273(14): p. 8137-44. 29. Zenke, F.T., et al., Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity. J Biol Chem, 1999. 274(46): p. 32565-73. 30. Malecka, K.A., Z. Szentpetery, and J.R. Peterson, Synergistic activation of p21-activated kinase 1 by phosphatidylinositol 4,5-bisphosphate and Rho GTPases. J Biol Chem, 2013. 288(13): p. 8887-97. 31. Barry, D.J., et al., Open source software for quantification of cell migration, protrusions, and fluorescence intensities. J Cell Biol, 2015. 209(1): p. 163-80. 32. Strochlic, T.I., et al., Phosphoinositides are essential coactivators for p21-activated kinase 1. Mol Cell, 2010. 40(3): p. 493-500. 33. Li, C.C., et al., ARL4D recruits Cytohesin-2/ARNO to modulate actin remodeling. Mol Biol Cell, 2007. 18(11): p. 4420-37. 34. Matsumoto, S., et al., A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures. EMBO J, 2014. 33(7): p. 702-18. 35. Patel, M., et al., The Arf Family GTPase Arl4A Complexes with ELMO Proteins to Promote Actin Cytoskeleton Remodeling and Reveals a Versatile Ras-binding Domain in the ELMO Proteins Family. J Biol Chem, 2011. 286(45): p. 38969-79. 36. Katoh, H. and M. Negishi, RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature, 2003. 424(6947): p. 461-4. 37. Manser, E., et al., A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature, 1994. 367(6458): p. 40-6. 38. Lei, M., et al., Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell, 2000. 102(3): p. 387-97. 39. Lu, W. and B.J. Mayer, Mechanism of activation of Pak1 kinase by membrane localization. Oncogene, 1999. 18(3): p. 797-806. 40. Price, L.S., et al., Activation of Rac and Cdc42 by integrins mediates cell spreading. Mol Biol Cell, 1998. 9(7): p. 1863-71. 41. Manser, E., et al., Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol, 1997. 17(3): p. 1129-43. 42. Stofega, M.R., et al., Constitutive p21-activated kinase (PAK) activation in breast cancer cells as a result of mislocalization of PAK to focal adhesions. Mol Biol Cell, 2004. 15(6): p. 2965-77. 43. Nayal, A., et al., Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics. J Cell Biol, 2006. 173(4): p. 587-9. 44. Symons, M., Adhesion signaling: PAK meets Rac on solid ground. Curr Biol, 2000. 10(14): p. R535-7. 45. Kimura, K., et al., Role of Rac1 in fibronectin-induced adhesion and motility of human corneal epithelial cells. Invest Ophthalmol Vis Sci, 2006. 47(10): p. 4323-9. 46. Sells, M.A., A. Pfaff, and J. Chernoff, Temporal and spatial distribution of activated Pak1 in fibroblasts. J Cell Biol, 2000. 151(7): p. 1449-58. 47. Sells, M.A., et al., Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr Biol, 1997. 7(3): p. 202-10. 48. Fan, X., et al., Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline. Neuron, 2003. 40(1): p. 113-27. 49. Chan, P.M., L. Lim, and E. Manser, PAK is regulated by PI3K, PIX, CDC42, and PP2Calpha and mediates focal adhesion turnover in the hyperosmotic stress-induced p38 pathway. J Biol Chem, 2008. 283(36): p. 24949-61. 50. Burbelo, P.D., D. Drechsel, and A. Hall, A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. J Biol Chem, 1995. 270(49): p. 29071-4. 51. Pirruccello, M., et al., A dimeric kinase assembly underlying autophosphorylation in the p21 activated kinases. J Mol Biol, 2006. 361(2): p. 312-26. 52. Parrini, M.C., et al., Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Mol Cell, 2002. 9(1): p. 73-83. 53. Buchwald, G., et al., Conformational switch and role of phosphorylation in PAK activation. Mol Cell Biol, 2001. 21(15): p. 5179-89. 54. Chong, C., et al., The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity. J Biol Chem, 2001. 276(20): p. 17347-53. 55. Mayhew, M.W., et al., Identification of phosphorylation sites in betaPIX and PAK1. J Cell Sci, 2007. 120(Pt 22): p. 3911-8. 56. Banerjee, M., et al., Pak1 phosphorylation on t212 affects microtubules in cells undergoing mitosis. Curr Biol, 2002. 12(14): p. 1233-9. 57. Sundberg-Smith, L.J., et al., Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. J Biol Chem, 2005. 280(3): p. 2055-64. 58. Thiel, D.A., et al., Cell cycle-regulated phosphorylation of p21-activated kinase 1. Curr Biol, 2002. 12(14): p. 1227-32. 59. Coniglio, S.J., S. Zavarella, and M.H. Symons, Pak1 and Pak2 mediate tumor cell invasion through distinct signaling mechanisms. Mol Cell Biol, 2008. 28(12): p. 4162-72. 60. Chiang, Y.T. and T. Jin, p21-Activated protein kinases and their emerging roles in glucose homeostasis. Am J Physiol Endocrinol Metab, 2014. 306(7): p. E707-22. 61. Parrini, M.C., et al., Dissecting activation of the PAK1 kinase at protrusions in living cells. J Biol Chem, 2009. 284(36): p. 24133-43. 62. Vadlamudi, R.K., et al., Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. Nat Cell Biol, 2002. 4(9): p. 681-90. 63. Kissil, J.L., et al., Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell, 2003. 12(4): p. 841-9. 64. Muralidharan-Chari, V., et al., ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol, 2009. 19(22): p. 1875-85. 65. Le Clainche, C. and M.F. Carlier, Regulation of actin assembly associated with protrusion and adhesion in cell migration. Physiol Rev, 2008. 88(2): p. 489-513. 66. Etienne-Manneville, S., Cdc42--the centre of polarity. J Cell Sci, 2004. 117(Pt 8): p. 1291-300. 67. Raftopoulou, M. and A. Hall, Cell migration: Rho GTPases lead the way. Dev Biol, 2004. 265(1): p. 23-32. 68. Ridley, A.J., Rho GTPase signalling in cell migration. Curr Opin Cell Biol, 2015. 36: p. 103-12. 69. Patel, M., et al., The Arf Family GTPase Arl4A Complexes with ELMO Proteins to Promote Actin Cytoskeleton Remodeling and Reveals a Versatile Ras-binding Domain in the ELMO Proteins Family. The Journal of Biological Chemistry, 2011. 286(45): p. 38969-38979. 70. Vadlamudi, R.K., et al., Regulatable expression of p21-activated kinase-1 promotes anchorage-independent growth and abnormal organization of mitotic spindles in human epithelial breast cancer cells. J Biol Chem, 2000. 275(46): p. 36238-44. 71. Kiosses, W.B., et al., A role for p21-activated kinase in endothelial cell migration. J Cell Biol, 1999. 147(4): p. 831-44. 72. Provenzani, A., et al., Global alterations in mRNA polysomal recruitment in a cell model of colorectal cancer progression to metastasis. Carcinogenesis, 2006. 27(7): p. 1323-33. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/21109 | - |
| dc.description.abstract | 細胞在遷移的過程中，需要協調多條信號通路，包括膜動力和細胞骨架重組。先前研究已顯示，小型GTP酶腺嘌呤核苷二磷酸核糖化因子相似蛋白四A(Arl4A)可以調節高爾基體的組織和肌動蛋白的細胞骨架重塑。然而，對於Arl4A在細胞遷移中所扮演的功能了解並不充足。在本篇論文中，我們發現Arl4A和絲氨酸/蘇氨酸蛋白激酶1 (Pak1)兩者扮演重要角色，通過相互協作募集彼此至質膜，來調控細胞的遷移。首先我們觀察到Arl4A會與Pak1直接性的相互結合，並以GTP依賴性方式將Pak1招募至質膜。在Arl4A缺少的細胞中，纖連蛋白(Fibronectin)所誘導的Pak1至細胞膜的程度有明顯減少。出乎意料的是，我們發現Pak1能招募胞質肉荳蔻酰化缺陷的Arl4A (G2A)突變體至細胞膜上，但與Arl4A結合缺陷型的Pak1就無法招募。此外， 我們發現，Arl4A-Pak1之間的結合，對於Arl4A誘導的細胞遷移是相當重要的。因此，我們推斷Arl4A和Pak1存在反饋調節，其中它們相互招募至細胞膜上造成Pak1的激活，從而通過直接相互作用調節細胞遷移。 | zh_TW |
| dc.description.abstract | Cell migration requires the coordination of multiple signaling pathways involved in membrane dynamics and cytoskeletal rearrangement. The Arf-like small GTPase Arl4A has been shown to modulate Golgi organization and actin cytoskeleton remodeling. However, evidence of the function of Arl4A in cell migration is insufficient. Here, we report that Arl4A acts with the serine/threonine protein kinase Pak1 to modulate cell migration through cooperative recruitment of each other to the plasma membrane. We first observed that Arl4A directly interacts with Pak1 and recruits Pak1 to the plasma membrane in a GTP-dependent manner. The fibronectin-induced Pak1 localization at the plasma membrane is reduced in Arl4A-depletion cells. Unexpectedly, we found that Pak1, but not Arl4A-binding-defective Pak1, can recruit a cytoplasmic myristoylation-deficient Arl4A-G2A mutant to the plasma membrane. Furthermore, we found that the Arl4A-Pak1 interaction, which is independent of Rac1 binding to Pak1, is critical for Arl4A-induced cell migration. Thus, we infer that there is feedback regulation between Arl4A and Pak1, in which they mutually recruit each other to the plasma membrane for Pak1 activation, thereby modulating cell migration through direct interaction. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T03:27:07Z (GMT). No. of bitstreams: 1 ntu-109-D02448003-1.pdf: 18779935 bytes, checksum: b56638287543fe76f29d98ed79bda727 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | TABLE of CONTENTS
口試委員會審定書…………………………………………………………...……. 1 Table of Contents…………………………………………………………..…….2 Abstract………………………………………………………………….......………6 中文摘要…………………………………………………….…………….....……….7 Introduction………………………………………………………...........…….…8 Material and Methods Cell culture........……………………………………………………...…………..11 Transient transfection in mammalian cells…………………...........11 Expression constructs…………………………………………….……..……12 SDS-PAGE and western blotting………....................................13 Antibodies………………………………………………………..........…………14 Generation and purification of recombinant proteins………………….........................................................…….15 In vitro binding assay………………………….…………………..….……….15 GST pull-down assay……………………………………..………..….………16 Rac1 activity pull-down……………………………………………..………..16 Co-immunoprecipitation……………………………………………..….……17 Immunofluorescence analysis……………………………………………….17 Transwell migration assay……………………………….………….…..……18 Quantification of membrane-targeting protein…………....………19 Pak1 immunoprecipitation kinase assay………………………………..19 Sub-cellular fractionation…………………………………………...……….20 Statistical analysis………………………………....……………….…………..21 Results A. Arl4A directly interacts with Pak1 through the Pak-PBD domain……............................................................................….22 B. Arl4A induces the plasma membrane localization of Pak1..24 C. Pak1 recruits cytoplasmic myristoylation-deficient Arl4A to the plasma membrane………..................................................…25 D. Cooperative recruitment of Arl4A and Pak1 to the plasma membrane is independent of the Pak1-Rac1 interaction and Pak1 kinase activity…............................................................…27 E. Arl4A-Pak1 interaction is required for Pak1-mediated Arl4A membrane targeting………………….........................................….28 F. Arl4A recruitment of Pak1 to the plasma membrane is independent of β-PIX, Nck, and PIP3 binding…………………...…29 G. Pak1 kinase activity is critical for Arl4A-induced cell migration……….........................................................................31 H. Cooperative recruitment of Arl4A and Pak1 to the plasma membrane plays an important role in Arl4A-induced cell migration……………….........................................................………31 I. Arl4A-Pak1-induced cell migration differs from Rac1-Pak1 signaling…...............................................................................33 J. Phosphorylation of T212 on Pak1 is important for Arl4A-Pak1 induced cell migration………………………….………………….....……...34 K. Arl4A decreased MLC-P level is not through Pak1…………...35 Discussion………………………………………………………………..…..…….36 Figures Fig. 1. Arl4A promoted Rac1 activity but did not further enhance Rac1 activity upon fibronectin stimulation ………………...…………44 Fig. 2. Arl4A directly interacts with the Pak1-PBD domain in a GTP-dependent manner……………………………..…….........….………45 Fig. 3. Interaction affinity of constitutive active Rac1 with Pak1-PBD is higher than Arl4A ………………………………………...…………46 Fig. 4. Arl4A directly interacts with Pak1 through the Pak1-PBD domain ....................................................................................47 Fig. 5. Arl4A expression induce cell protrusion morphology …48 Fig. 6. Arl4A recruits Pak1 to the plasma membrane …...........49 Fig. 7. Arl4A recruits β-PIX, and GIT to the plasma membrane …………......................................................................................51 Fig. 8. Detection of Arl4 and Pak isoforms in cancer cell lines via western blotting ………………………........................………………52 Fig. 9. Knockdown of Arl4A affect Pak1 recruit to the plasma membrane by fibronectin ……………………………………………..………53 Fig. 10. Pak1 and Arl4A recruit each other to the plasma membrane ………..………………………………………………………………...54 Fig. 11. Pak1 can interact with Arl4A-G2A …………………………...55 Fig. 12. Alignment protein sequence of Pak1 and Pak2………. 56 Fig. 13. Arl4A and Arl4D interact with Pak-PBD, but not Arl4C ………………..………………………………………………………………...……….57 Fig. 14. Both Arl4A and Arl4D can induce Pak1/2 localization to the plasma membrane ……………………………………......………….…59 Fig. 15. The Pak1-Arl4A cooperative recruitment to the plasma membrane is independent of the Pak1-Rac1 interaction and Pak1 kinase activity…………………….......……………………..……………60 Fig. 16. Mapping the amino acids responsible for the Arl4A-Pak1 Interaction…………………………………….........…….………………..61 Fig. 17. Pak1-m5 mutant block Arl4A and affect Rac1 interaction with Pak1………………………………………..............…………………..…….63 Fig. 18. Pak1 recruited Arl4A to the plasma membrane in an interaction-dependent manner ………………………........…………….64 Fig. 19. The recruitment of Pak1 to the plasma membrane by Arl4A is independent of Robo1 and b-Pix ………….......…….……..65 Fig. 20. Arl4A recruits Pak1 to the plasma membrane is independent of Nck and PIP3 binding ...…………………….…...……67 Fig. 21. Arl4A and Pak1 promotes cell migration …….…….………68 Fig. 22. Arl4A-Pak1 interaction is required for the migration of C33A cells...............................................................................69 Fig. 23. Interplay between Arl4A-Pak1 is required for Arl4A-induced cell migration………………………………………...….……….……71 Fig. 24. Arl4A induced cell migration is not Rac1-Pak1 interaction dependent……………………...........……………………….….72 Fig. 25. Arl4A-Pak1-induced cell migration differs from Rac1-Pak1 signaling……………………...........………………………………….……73 Fig. 26. Arl4A is involved in fibronectin-induced Pak1 phosphorylation…...........…………………………………………….………..74 Fig. 27. Arl4A indirectly activates Pak1 through an unidentified kinase associated Arl4A ………………………………..……………..…..…75 Fig. 28. Identification of the differentially expressed phosphorylation sites on Pak1-WT in Arl4A-WT-expressing cells by mass spectrometry..……………………………………….……….76 Fig. 29. Phosphorylation of Pak1 T212 is important for Arl4A-Pak1 induced cell migration…………………………………………..….....77 Fig. 30. Expression of active Arl4A decreases MLC phosphorylation…….……………………………………………………..……...78 Fig. 31. Arl4A-Pak1 interaction is required for Pak1-mediated MLC-phosphorylation…………………………………...........…..………...79 Fig. 32. Arl4A-induced MLC-P decrease is independent on Pak1 and Arf6..………………………………………………………………..……………80 Fig. 33. Summary of this study ……………..………………....….………81 Fig. 34. Erk phosphorylation changes in Arl4A expressing and knock-downed cells.………….………………….........………...…..……...82 Fig. 35. Arl4A and Rac1 compete the interaction site on Pak-PBD…….………………………………………………………………………………..84 Fig. 36. Arl4A is a short half-life protein ………………..………....…84 Fig. 37. Unsolved questions and future plan …………..……………85 Table Table 1. siRNA oligonucleotide information ……….……...…...……86 References………………………………………………………………….....……87 | |
| dc.language.iso | en | |
| dc.title | Arl4A和Pak1協同招集至細胞膜有助於維持Pak1活化並促進細胞爬行 | zh_TW |
| dc.title | Cooperative recruitment of Arl4A and Pak1 to the plasma membrane contributes to sustained Pak1 activation for cell migration | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 陳鴻震,陳瑞華,張智芬,周祖述,劉雅雯 | |
| dc.subject.keyword | Ras家族,ADP-核糖基化因子,小型GTP?,細胞遷移,絲氨酸/蘇氨酸蛋白激?1, | zh_TW |
| dc.subject.keyword | Ras superfamily,ADP-ribosylation factor,GTPase,Cell migration,Pak1, | en |
| dc.relation.page | 91 | |
| dc.identifier.doi | 10.6342/NTU202000060 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-01-10 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-109-1.pdf 目前未授權公開取用 | 18.34 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。