Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/22805
DC FieldValueLanguage
dc.contributor余兆松zh_TW
dc.contributorJau-Song Yuen_US
dc.contributor林赫zh_TW
dc.contributorHo Linen_US
dc.contributor.advisor陳鴻震zh_TW
dc.contributor.advisorHong-Chen Chenen_US
dc.contributor.author潘羿汝zh_TW
dc.contributor.authorPan, Yi-Ruen_US
dc.contributor.other中興大學zh_TW
dc.date2009zh_TW
dc.date.accessioned2014-06-06T07:18:43Z-
dc.date.available2014-06-06T07:18:43Z-
dc.identifierU0005-3007200819360600zh_TW
dc.identifier.citationAllavena, P., Paganin, C., Martin-Padura, I., Peri, G., Gaboli, M., Dejana, E., Marchisio, P. C. and Mantovani, A. (1991). Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium. J. Exp. Med. 173, 439-448. Almeida, E.A., Ilić, D., Han, Q., Hauck, C. R., Jin, F., Kawakatsu, H., Schlaepfer, D. D. and Damsky, C. H. (2000). Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase. J. Cell Biol. 149, 741-754. Amato, P. A., Unanue, E. R. and Taylor, D. L. (1983). Distribution of actin in spreading macrophages: a comparative study on living and fixed cells. J. Cell Biol. 96, 750-761. Antón, I. M., Jones, G. E., Wandosell, F., Geha, R. and Ramesh, N. (2007). WASP-interacting protein (WIP): working in polymerisation and much more. Trends Cell Biol. 17, 555-562. Babb, S. G., Matsudaira, P., Sato, M., Correia, I. and Lim, S. S. (1997). Fimbrin in podosomes of monocyte-derived osteoclasts. Cell Motil. Cytoskeleton 37, 308-325. Badowski, C., Pawlak, G., Grichine, A., Chabadel, A., Oddou, C., Jurdic, P., Pfaff, M., Albigès-Rizo, C. and Block, M. R. (2008). Paxillin Phosphorylation Controls Invadopodia/Podosomes Spatiotemporal Organization. Mol. Biol. Cell 19, 633-645. Bharti, S., Inoue, H., Bharti, K., Hirsch, D. S., Nie, Z., Yoon, H. Y., Artym, V., Yamada, K. M., Mueller, S. C., Barr, V. A. and Randazzo, P. A. (2007). Src-dependent phosphorylation of ASAP1 regulates podosomes. Mol. Cell Biol. 27, 8271-8283. Bolen, J. B., Veillette, A., Schwartz, A. M., DeSeau, V. and Rosen, N. (1987). Activation of pp60c-src protein kinase activity in human colon carcinoma. Proc. Natl. Acad. Sci. USA 84, 2251-2255. Brábek, J., Constancio, S. S., Shin, N. Y., Pozzi, A., Weaver, A. M. and Hanks, S. K. (2004). CAS promotes invasiveness of Src-transformed cells. Oncogene 23, 7406-7415. Brábek, J., Constancio, S. S., Siesser, P. F., Shin, N. Y., Pozzi, A. and Hanks, S. K. (2005). Crk-associated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRC-transformed cells. Mol. Cancer Res. 3, 307-315. Bruzzaniti, A., Neff, L., Sanjay, A., Horne, W. C., De-Camilli, P. and Baron, R. (2005). Dynamin forms a Src kinase-sensitive complex with Cbl and regulates podosomes and osteoclast activity. Mol. Biol. Cell 16, 3301-3313. Burgstaller, G. and Gimona, M. (2004). Actin cytoskeleton remodelling via local inhibition of contractility at discrete microdomains. J. Cell Sci. 117, 223-231. Burns, S., Thrasher, A. J., Blundell, M. P., Machesky, L. and Jones, G. E. (2001). Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WAS protein, and differentiation. Blood 98, 1142-1149. Calle, Y., Chou, H. C., Thrasher, A. J. and Jones, G. E. (2004). Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells. J. Pathol. 204, 460-469. Chabadel, A., Bañon-Rodríguez, I., Cluet, D., Rudkin, B. B., Wehrle-Haller, B., Genot, E., Jurdic, P., Anton, I. M. and Saltel, F. (2007). CD44 and beta3 integrin organize two functionally distinct actin-based domains in osteoclasts. Mol. Biol. Cell 18, 4899-4910. Chellaiah, M., Kizer, N., Silva, M., Alvarez, U., Kwiatkowski, D. and Hruska, K. A. (2000). Gelsolin-deficiency blocks podosome assembly and produces increased bone mass and strength. J. Cell Biol. 148, 665-678. Chellaiah, M. A., Biswas, R. S., Yuen, D., Alvarez, U. M. and Hruska, K. A. (2001). Phosphatidylinositol 3,4,5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin. J. Biol. Chem. 276, 47434-47444. Chen, W. T., Olden, K., Bernard, B. A. and Chu, F. F. (1984). Expression of transformation-associated protease(s) that degrade fibronectin at cell contact sites. J. Cell Biol. 98, 1546-1555. Chou, H. C., Antón, I. M., Holt, M. R., Curcio, C., Lanzardo, S., Worth, A., Burns, S., Thrasher, A. J., Jones, G. E. and Calle, Y. (2006). WIP regulates the stability and localization of WASP to podosomes in migrating dendritic cells. Curr. Biol. 16, 2337-2344. Correia, I., Chu, D., Chou, Y. H., Goldman, R. D. and Matsudaira, P. (1999). Integrating the actin and vimentin cytoskeletons. Adhesion dependent formation of fimbrin-vimentin complexes in macrophages. J. Cell Biol. 146, 831-842. Cougoule, C., Carréno, S., Castandet, J., Labrousse, A., Astarie-Dequeker, C., Poincloux, R., Le-Cabec, V. and Maridonneau-Parini, I. (2005). Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes. Traffic 6, 682-694. Czernilofsky, A.P., Levinson, A. D., Varmus, H.. E. Bishop, J. M.. Tischer, E. and Goodman. H. (1983). Corrections to the nucleotide sequence of the src gene of Rous sarcoma virus. Nature 301, 736-738. Defilippi, P., Di-Stefano, P. and Cabodi, S. (2006). p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol. 16, 257-263. Delaissé, J. M., Engsig, M. T., Everts, V., del Carmen Ovejero, M., Ferreras, M., Lund, L., Vu, T. H., Werb, Z., Winding, B., Lochter, A., Karsdal, M. A., Troen, T., Kirkegaard, T., Lenhard, T., Heegaard, A. M., Neff, L., Baron, R. and Foged, N. T. (2000). Proteinases in bone resorption: obvious and less obvious roles. Clin. Chim. Acta. 291, 223-234. Destaing, O., Saltel, F., Géminard, J. C., Jurdic, P. and Bard, F. (2003). Podosomes display actin turnover and dynamic self-organization in osteoclasts expressing actin-green fluorescent protein. Mol. Biol. Cell 14, 407-416. Destaing, O., Saltel, F., Gilquin, B., Chabadel, A., Khochbin, S., Ory, S. and Jurdic, P. (2005). A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts. J. Cell Sci. 118, 2901-2911. Destaing, O., Sanjay, A., Itzstein, C., Horne, W. C., Toomre, D., De-Camilli, P. and Baron, R. (2008). The Tyrosine Kinase Activity of c-Src Regulates Actin Dynamics and Organization of Podosomes in Osteoclasts. Mol. Biol. Cell 19, 394-404. Duong, L. T. and Rodan, G. A. (2000). PYK2 is an adhesion kinase in macrophages, localized in podosomes and activated by beta(2)-integrin ligation. Cell Motil. Cytoskeleton 47, 174-188. Eves, R., Webb, B. A., Zhou, S. and Mak, A. S. (2006). Caldesmon is an integral component of podosomes in smooth muscle cells. J. Cell Sci. 119, 1691-1702. Fincham, V.J., Chudleigh, A. and Frame, M. C. (1999). Regulation of p190 Rho-GAP by v-Src is linked to cytoskeletal disruption during transformation. J. Cell Sci. 112, 947-956. Frame, M. C. (2002). Src in cancer: deregulation and consequences for cell behaviour. Biochim. Biophys. Acta. 1602, 114-130. Gatesman, A., Walker, V. G., Baisden, J. M., Weed, S. A. and Flynn, D. C. (2004). Protein kinase Calpha activates c-Src and induces podosome formation via AFAP-110. Mol. Cell Biol. 24, 7578-7597. Gil-Henn, H., Destaing, O., Sims, N. A., Aoki, K., Alles, N., Neff, L., Sanjay, A., Bruzzaniti, A., De Camilli, P., Baron, R. and Schlessinger, J. (2007). Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) mice. J. Cell Biol. 178, 1053-1064. Gavazzi, I., Nermut, M. V. and Marchisio, P. C. (1989). Ultrastructure and gold-immunolabelling of cell-substratum adhesions (podosomes) in RSV-transformed BHK cells. J. Cell Sci. 94, 85-99. Gimona, M., Buccione, R., Courtneidge, S. A. and Linder, S. (2008). Assembly and biological role of podosomes and invadopodia. Curr. Opin. Cell Biol. 20, 235-241. Goicoechea, S., Arneman, D., Disanza, A., Garcia-Mata, R., Scita, G. and Otey, C. A. (2006). Palladin binds to Eps8 and enhances the formation of dorsal ruffles and podosomes in vascular smooth muscle cells. J. Cell Sci. 119, 3316-3324. Goldberg, G. S., Alexander, D. B., Pellicena, P., Zhang, Z. Y., Tsuda, H. and Miller, W. T. (2003). Src phosphorylates Cas on tyrosine 253 to promote migration of transformed cells. J. Biol. Chem. 278, 46533-46540. Gringel, A., Walz, D., Rosenberger, G., Minden, A., Kutsche, K., Kopp, P. and Linder, S. (2006). PAK4 and alphaPIX determine podosome size and number in macrophages through localized actin regulation. J. Cell Physiol. 209, 568-579. Gu, Z., Kordowska, J., Williams, G. L., Wang, C. L. and Hai, C. M. (2007). Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells. Exp. Cell Res. 313, 849-866. Hai, C. M., Hahne, P., Harrington, E. O. and Gimona, M. (2002). Conventional protein kinase C mediates phorbol-dibutyrate-induced cytoskeletal remodeling in a7r5 smooth muscle cells. Exp. Cell Res. 280, 64-74. Hilenski, L. L., Terracio, L. and Borg, T. K. (1991). Myofibrillar and cytoskeletal assembly in neonatal rat cardiac myocytes cultured on laminin and collagen. Cell Tissue Res. 264, 577-587. Hoelper, P., Faust, D., Oesch, F. and Dietrich, C. (2005). Evaluation of the role of c-Src and ERK in TCDD-dependent release from contact-inhibition in WB-F344 cells. Arch. Toxicol. 79, 201-207. Hood, J. D. and Cheresh, D. A. (2002). Role of integrins in cell invasion and migration. Nat. Rev. Cancer. 2, 91-100. Irby, R. B. and Yeatman, T. J. (2000). Role of Src expression and activation in human cancer. Oncogene 19, 5636-5642. Kadono, Y., Okada, Y., Namiki, M., Seiki, M. and Sato, H. (1998). Transformation of epithelial Madin-Darby canine kidney cells with p60 (v-src) induces expression of membrane-type 1 matrix metalloproteinase and invasiveness. Cancer Res. 58, 2240-2244. Kopp, P., Lammers, R., Aepfelbacher, M., Woehlke, G., Rudel, T., Machuy, N., Steffen, W. and Linder, S. (2006). The kinesin KIF1C and microtubule plus ends regulate podosome dynamics in macrophages. Mol. Biol. Cell 17, 2811-2823. Krits, I., Wysolmerski, R. B., Holliday, L. S. and Lee, B. S. (2002). Differential localization of myosin II isoforms in resting and activated osteoclasts. Calcif. Tissue Int. 71, 530-538. Lakkakorpi, P. T., Wesolowski, G., Zimolo, Z., Rodan, G. A. and Rodan, S. B. (1997). Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading. Exp. Cell Res. 237, 296-306. Lehto, V. P., Hovi, T., Vartio, T., Badley, R. A. and Virtanen, I. (1982). Reorganization of cytoskeletal and contractile elements during transition of human monocytes into adherent macrophages. Lab. Invest. 47, 391-399. Lewis, A. K. and Bridgman, P. C. (1992). Nerve growth cone lamellipodia contain two populations of actin filaments that differ in organization and polarity. J. Cell Biol. 119, 1219-1243. Lim, Y., Han, I., Jeon, J., Park, H., Bahk, Y. Y. and Oh, E. S. (2004). Phosphorylation of Focal Adhesion Kinase at Tyrosine 861 Is Crucial for Ras Transformation of Fibroblasts. J. Biol. Chem. 279, 29060-29065. Linder, S., Nelson, D., Weiss, M. and Aepfelbacher, M. (1999). Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages. Proc. Natl. Acad. Sci. USA 96, 9648-9653. Linder, S., Higgs, H., Hüfner, K., Schwarz, K., Pannicke, U. and Aepfelbacher, M. (2000). The polarization defect of Wiskott-Aldrich syndrome macrophages is linked to dislocalization of the Arp2/3 complex. J. Immunol. 165, 221-225. Linder, S. and Aepfelbacher, M. (2003). Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol. 13, 376-385. Linder, S. (2007). The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends Cell Biol. 17, 107-117. Liu, Y., Loijens, J. C., Martin, K. H., Karginov, A. V. and Parsons, J. T. (2002). The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. Mol. Biol. Cell. 13, 2147-2156. Luxenburg, C., Geblinger, D., Klein, E., Anderson, K., Hanein, D., Geiger, B. and Addadi, L. (2007). The architecture of the adhesive apparatus of cultured osteoclasts: from podosome formation to sealing zone assembly. PLoS ONE. 2, e179. Marchisio, P. C., Cirillo, D., Naldini, L., Primavera, M. V., Teti, A. and Zambonin-Zallone, A. (1984). Cell-substratum interaction of cultured avian osteoclasts is mediated by specific adhesion structures. J. Cell Biol. 99, 1696-1705. Marchisio, P. C., Cirillo, D., Teti, A., Zambonin-Zallone, A. and Tarone, G. (1987). Rous sarcoma virus-transformed fibroblasts and cells of monocytic origin display a peculiar dot-like organization of cytoskeletal proteins involved in microfilamentmembrane interactions. Exp. Cell Res. 169, 202-214. Martin, G. S. (1970). Rous Sarcoma Virus: a Function required for the Maintenance of the Transformed State. Nature 227, 1021-1023. Minkin, C. and Marinho, V. C. (1999). Role of the osteoclast at the bone-implant interface. Adv. Dent. Res. 13, 49-56. Mitra, S. K., Hanson, D. A. and Schlaepfer, D. D. (2005). Focal adhesion kinase: in command and control of cell motility. Nat. Rev. Mol. Cell Biol. 6, 56-68. Mitra, S. K., Mikolon, D., Molina, J. E., Hsia, D. A., Hanson, D. A., Chi, A., Lim, S. T., Bernard-Trifilo, J. A., Ilic, D., Stupack, D. G., Cheresh, D. A. and Schlaepfer, D. D. (2006). Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors. Oncogene 25, 5969-5984. Mizutani, K., Miki, H., He, H., Maruta, H. and Takenawa, T. (2002). Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts. Cancer Res. 62, 669-974. Morita, T., Mayanagi, T., Yoshio, T. and Sobue, K. (2007). Changes in the balance between caldesmon regulated by p21-activated kinases and the Arp2/3 complex govern podosome formation. J. Biol. Chem. 282, 8454-8463. Nakamoto, T., Sakai, R., Honda, H., Ogawa, S., Ueno, H., Suzuki, T., Aizawa, S., Yazaki, Y. and Hirai, H. (1997). Requirements for localization of p130cas to focal adhesions. Mol. Cell Biol. 17, 3884-3897. Nermut, M. V., Eason, P., Hirst, A. and Kellie, S. (1991). Cell/substratum adhesions in RSV-transformed rat fibroblasts. Exp. Cell Res. 193, 382-397. Ochoa, G. C., Slepnev, V. I., Neff, L., Ringstad, N., Takei, K., Daniell, L., Kim, W., Cao, H., McNiven, M., Baron, R. and De Camilli, P. (2000). A functional link between dynamin and the actin cytoskeleton at podosomes. J. Cell Biol. 150, 377-389. Ory, S., Munari-Silem, Y., Fort, P. and Jurdic, P. (2000). Rho and Rac exert antagonistic functions on spreading of macrophage-derived multinucleatedcells and are not required for actin fiber formation. J. Cell Sci. 113, 1177-1188. Owen, J. D., Ruest, P. J., Fry, D. W. and Hanks, S. K. (1999). Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto- and activation loop phosphorylation sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2. Mol. Cell Biol. 19, 4806-4818. Owens, L. V., Xu, L., Craven, R. J., Dent, G. A., Weiner, T. M., Kornberg, L., Liu, E. T. and Cance, W. G. (1995). Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res. 55, 2752-2755. Page-McCaw, A., Ewald, A. J. and Werb, Z. (2007). Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell Biol. 8, 221-233. Palazzo, A. F., Eng, C. H., Schlaepfer, D. D., Marcantonio, E. E. and Gundersen, G. G. (2004). Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science 303, 836-839. Park, S. J., Suetsugu, S. and Takenawa, T. (2005). Interaction of HSP90 to N-WASP leads to activation and protection from proteasome-dependent degradation. EMBO J. 24, 1557-1570. Parsons, J. T. (2003). Focal adhesion kinase: the first ten years. J. Cell Sci. 116, 1409-1416. Pellicena, P. and Miller, W. T. (2002). Coupling kinase activation to substrate recognition in SRC-family tyrosine kinases. Front Biosci. 7, 256-267. Pfaff, M. and Jurdic, P. (2001). Podosomes in osteoclast-like cells: structural analysis and cooperative roles of paxillin, proline-rich tyrosine kinase 2 (Pyk2) and integrin alphaVbeta3. J. Cell Sci. 114, 2775-2786. Poincloux, R., Cougoule, C., Daubon, T., Maridonneau-Parini, I. and Le Cabec, V. (2007). Tyrosine-phosphorylated STAT5 accumulates on podosomes in Hck-transformed fibroblasts and chronic myeloid leukemia cells. J. Cell Physiol. 213, 212-220. Rous, P. (1911). A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J. Exp. Med. 13, 397-411. Saltel, F., Destaing, O., Bard, F., Eichert, D. and Jurdic, P. (2004). Apatite-mediated actin dynamics in resorbing osteoclasts. Mol. Biol. Cell 15, 5231-541. Salter, M. W. and Kalia, L. V. (2004). Src kinases: a hub for NMDA receptor regulation. Nat. Rev. Neurosci. 5, 317-328. Sato, T., del Carmen Ovejero, M., Hou, P., Heegaard, A. M., Kumegawa, M., Foged, N. T. and Delaissé, J. M. (1997). Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts. J. Cell Sci. 110, 589-596. Schaller, M. D. and Parsons, J. T. (1995). pp125FAK-dependent tyrosine phosphorylation of paxillin creates a high-affinity binding site for Crk. Mol. Cell Biol. 15, 2635-2645. Seals, D. F., Azucena, E. F., Pass, I., Tesfay, L., Gordon, R., Woodrow, M., Resau, J. H. and Courtneidge, S. A. (2005). The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cell. Cancer Cell 7, 155-165. Serrels, B., Serrels, A., Brunton, V. G., Holt, M., McLean, G. W., Gray, C. H., Jones, G. E. and Frame, M. C. (2007). Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. Nat. Cell Biol. 9, 1046-1056. Stickel, S. K. and Wang, Y. L. (1987). Alpha-actinin-containing aggregates in transformed cells are highly dynamic structures. J. Cell Biol. 104, 1521-1526. Sun, H. Q., Yamamoto, M., Mejillano, M. and Yin, H. L. (1999). Gelsolin, a multifunctional actin regulatory protein. J. Biol. Chem. 274, 33179-33182. Svitkina, T. M. and Borisy, G. G. (1999). Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J. Cell Biol. 145, 1009-1026. Symons, M. and Settleman, J. (2000). Rho family GTPases: more than simple switches. Trends Cell Biol. 10, 415-419. Takeya, T. and Hanafusa, H. (1983). Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus. Cell 32, 881-890. Tanaka, J., Watanabe, T., Nakamura, N. and Sobue, K. (1993). Morphological and biochemical analyses of contractile proteins (actin, myosin, caldesmon and tropomyosin) in normal and transformed cells. J. Cell Sci. 104, 595-606. Tarone, G., Cirillo, D., Giancotti, F. G., Comoglio, P. M. and Marchisio, P. C. (1985). Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes. Exp. Cell Res. 159, 141-157. Tatin, F., Varon, C., Génot, E. and Moreau, V. (2006). A signalling cascade involving PKC, Src and Cdc42 regulates podosome assembly in cultured endothelial cells in response to phorbol ester. J. Cell Sci. 119, 769-781. Teti, A., Grano, M., Carano, A., Colucci, S. and Zambonin Zallone, A. (1989). Immunolocalization of beta 3 subunit of integrins in osteoclast membrane. Boll. Soc. Ital. Biol. Sper. 65, 1031-1037. Teti, A., Blair, H. C., Schlesinger, P., Grano, M., Zambonin-Zallone, A., Kahn, A. J., Teitelbaum, S. L. and Hruska, K. A. (1989). Extracellular protons acidify osteoclasts, reduce cytosolic calcium, and promote expression of cell-matrix attachment structures. J. Clin. Invest. 84, 773-780. Thomas, S. M. and Brugge, J. S. (1997). Cellular functions regulated by Src family kinases. Annu. Rev. Cell Dev. Biol. 13, 513-609. Tsuboi, S. (2007). Requirement for a complex of Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein in podosome formation in macrophages. J. Immunol. 178, 2987-2995. Vallés, A. M., Beuvin, M. and Boyer, B. (2004). Activation of Rac1 by paxillin-Crk-DOCK180 signaling complex is antagonized by Rap1 in migrating NBT-II cells. J. Biol. Chem. 279, 44490-44496. West, M. A., Prescott, A. R., Eskelinen, E. L., Ridley, A. J. and Watts, C. (2000). Rac is required for constitutive macropinocytosis by dendritic cells but does not control its downregulation. Curr. Biol. 10, 839-848. Wu, X., Gan, B., Yoo, Y. and Guan, J. L. (2005). FAK-mediated src phosphorylation of endophilin A2 inhibits endocytosis of MT1-MMP and promotes ECM degradation. Dev. Cell 9, 185-196. Yeatman, T. J. (2004). A renaissance for SRC. Nat. Rev. Cancer 4, 470-480. Zambonin-Zallone, A., Teti, A., Grano, M., Rubinacci, A., Abbadini, M., Gaboli, M. and Marchisio, P. C. (1989). Immunocytochemical distribution of extracellular matrix receptors in human osteoclasts: A b3 integrin is colocalized with vinculin and talin in the podosomes of osteoclastoma giant cells. Exp. Cell Res. 182, 645-652. Zhang, D., Udagawa, N., Nakamura, I., Murakami, H., Saito, S., Yamasaki, K., Shibasaki, Y., Morii, N., Narumiya, S. and Takahashi, N. (1995). The small GTP-binding protein, rho p21, is involved in bone resorption by regulating cytoskeletal organization in osteoclasts. J. Cell Sci. 108, 2285-2292.zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/22805-
dc.description.abstractPodosomes是一個以actin為主體的結構,主要存在於細胞的腹面,其功能為促進細胞外基質的瓦解。Podosomes除了存在於v-Src轉型的纖維母細胞 (v-Src-transformed fibroblast) 之外,類似的結構還常被發現存於噬骨細胞、樹突細胞及一些具組織侵犯性的癌症細胞,在v-Src轉型纖維母細胞中的podosomes,常圍成環形結構,稱之為podosome rings。Focal adhesion kinase (FAK) 主要位於focal adhesions的酪氨酸激酶,已知FAK會與Src的結合。在本篇研究中,我們發現在v-Src轉型的老鼠胚胎纖維母細胞中具有podosome rings的結構,但其不存在於v-Src轉型的FAK基因剔除 (FAK-/-) 的老鼠胚胎纖維母細胞中,進一步觀察其結構特性發現podosome rings是一個外徑約15 μm、內徑約7 μm及高約18 μm的柱狀結構。為了探討FAK在podosome rings形成過程中所扮演的角色,在v-Src轉型的FAK基因剔除的老鼠胚胎纖維母細胞中,建立可誘導蛋白表現的系統,在沒有FAK表現的情況下,v-Src無法促進podosome rings形成,在有FAK表現的情況下,會有podosome rings聚集的現象,並隨著FAK表現量增加,形成podosome rings的細胞比例越高,podosome rings形成過程不需要倚賴新的 (de novo) 基因表現,且FAK及Src都會聚集在podosome rings上,除此之外,利用影像追蹤發現podosome rings存在的時間大約10~30分鐘,進一步利用FAK Y397F及Y576/577F的突變株發現,FAK的自我磷酸化位置Y397及FAK的激酶活性對於podosome rings形成是必須的。綜合以上的結果,我們除了更詳細描述在v-Src轉型纖維母細胞中的podosomes rings,也發現到podosome rings形成過程中FAK必須存在。zh_TW
dc.description.abstractPodosomes are actin-enriched structures, which represent convolutions and extensions of the ventral surface plasma membrane. The function of podosomes is to decompose extracellular matrix. Following the discovery of podosomes in v-Src-transformed cells, similar structures were identified in osteoclasts, macrophages, and certain invasive human cancer cells. Podosomes in v-Src-transformed fibroblasts are often found to assemble into prominent, ring-shaped structures called podosome rings. Focal adhesion kinase (FAK), a cellular tyrosine kinase mainly localized in focal adhesions, is known to interact with Src. In this study, we found that v-Src induced podosome rings formation in mouse embryo fibroblasts, but failed to do so in their FAK-null counterparts. The reconstituted three-dimensional images revealed that podosome rings are actin-enriched hollow-tube structures approximately 15 μm in diameter with 7 μm lumen and 18 μm in height. To further examine the role of FAK in the formation of podosome rings, an inducible FAK expression system was established in v-Src-transformed FAK-null cells. Without FAK induction, v-Src was not sufficient to form podosome rings. Conversely, the assembly of podosome rings was triggered upon FAK induction, closely associated with the expression level of FAK. In addition, the assembly of podosome rings did not rely on de novo gene expression. FAK and Src were found to co-localize with the F-actin at podosome rings. Using time-lapse video microscopy, the life span of podosome rings was estimated to be 10-30 min. Furthermore, the FAK autophosphorylation site Y397 and FAK activity are essential for podosome ring formation. Taken together, our results not only depict the formation of v-Src-induced podosome rings in more detail but also suggest an essential role for FAK in this process.en_US
dc.description.tableofcontents中文摘要……………………………………………….……….………………………i 英文摘要……………………………………………………….……………….………ii Ⅰ 文獻探討…………………………………………………….………….…………..1 Ⅱ 材料與方法………………………………….…………………………...………....5 實驗材料 一、細胞株………………………………………………….……………..……….5 二、質體…………………………………………….………………………..…….5 三、抗體………………………………………………………….………..……….5 四、藥品……………………………………………….…………………………...6 五、儀器……………………………………………………….…………………...7 實驗方法 一、細胞培養…………………………………………………………………….…7 二、細胞株的建立……………………………………………………………….…7 三、細胞蛋白質之萃取………………………………………………………….…7 四、西方轉印法………………………………………………………………….…8 五、免疫沈澱法………………………………………………………………….…8 六、Matrigel侵犯分析……………………………………………………………..8 七、蛋白免疫螢光染色………………………………………………………….…9 八、影像追蹤…………………………………………………………………….…9 九、細胞外基質瓦解分析……………………………………………………….…9 Ⅲ 結果 一、FAK+/+/v-Src細胞中有actin rings的特殊結構,但此結構不存於FAK-/-/v-Src細胞中…………………………..…………………….………………..…..….20 二、v-Src表現細胞中的actin dots為individual podosomes,而在FAK+/+/ v-Src細胞中的actin rings podosomrings…………………………..……11 三、Podosome rings是一個由actin所組成的柱狀結構………………..……11 四、FAK表現量越高podosome rings形成比例越高………………….….….11 五、Podosome rings的形成不需要新的 (de nove) 基因表現…….….....….12 六、FAK、cortactin、Src和paxillin皆聚集在podosome rings上……...….12 七、Podosome rings的half life約10~15分鐘……………………………....13 八、FAK的激酶活性及FAK的自我磷酸化位置 Y397貢獻於podosome rings的形成…………………..……………………………………….…………..13 Ⅳ 討論………………………………………………………..………………………15 Ⅴ 參考文獻……………………………………………………..……………………19 Ⅵ 附圖…………………………………………………………..……………………28 Ⅶ 附錄 附錄表………………………………………………………….……….…………36 附錄圖……………………………………………………………….…….………40zh_TW
dc.language.isoen_USzh_TW
dc.publisher生命科學系所zh_TW
dc.relation.urihttp://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-3007200819360600en_US
dc.subjectFocal adhesion kinaseen_US
dc.subject酪氨酸基酶zh_TW
dc.subjectSrcen_US
dc.subjectpoodosomeen_US
dc.titleFocal Adhesion Kinase對於致癌基因Src引起podosome rings形成是必要的zh_TW
dc.titleFocal Adhesion Kinase Is Essential for Oncogenic Src-induced Podosome Ringsen_US
dc.typeThesis and Dissertationzh_TW
item.languageiso639-1en_US-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.openairetypeThesis and Dissertation-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextno fulltext-
Appears in Collections:生命科學系所
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