Browse > Article
http://dx.doi.org/10.5487/TR.2008.24.1.001

Phosphoinositides Signaling and Epithelial-to-Mesenchymal Transition: Putative Topic for Basic Toxicological Research  

Lee, Chang-Ho (Department of Pharmacology and Biomedical Science, College of Medicine, Hanyang University)
Publication Information
Toxicological Research / v.24, no.1, 2008 , pp. 1-9 More about this Journal
Abstract
Ptdlns(4,5)$P_2$ is a key cellular phosphoinositide that localizes in separate and distinctive pools in subcellular membrane and vesicular compartments. In membranes, Ptdlns(4,5)$P_2$ acts as a precursor to second messengers and is itself a main signaling and targeting molecule. Specific subcellular localization of type I PIP kinases directed by interacting with specific targeting module differentiates Ptdlns(4,5)$P_2$ production in a spatial and temporal manner. Several lines of evidences support the idea that Ptdlns(4,5)$P_2$ is generated in very specific pools in a spatial and temporal manner or by feeding Ptdlns(4,5)$P_2$ directly to effectors. In this concept, the interaction of PIPKI isoforms with a specific targeting module to allow precise subcellular targeting modulates highly specific Ptdlns(4,5)$P_2$ synthesis and channeling overall effectors. For instance, localization of PIPKI${\gamma}$661 to focal adhesions by an interaction with talin results in spatial and temporal production of Ptdlns(4,5)$P_2$, which regulates EGF-stimulated directional cell migration. In addition, Type $I{\gamma}$ PIPK is targeted to E-cadherin in cell adherence junction and plays a role in controlling dynamics of cell adherence junction and endocytosis of E-cadherin. Characterizing how PIP kinase isoforms are regulated by interactions with their targeting modules, as well as the mechanisms by which their product, Ptdlns(4,5)$P_2$, exerts its effects on cellular signaling processes, is crucial to understand the harmonized control of numerous cellular signaling pathways. Thus, in this review the roles of the Ptdlns(4)P(5) kinases and Ptdlns(4,5)$P_2$ were described and critically reviewed in terms of regulation of the E-cadherin trafficking, cell migration, and formation of cell adherence junction which is indispensable and is tightly controlled in epithelial-to-mesenchymal transition process.
Keywords
PIP kinases; PIPKI${\gamma}$661; E-cadherin; EMT; Adherence Junction;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Ridley, A.J., Paterson, H.F., Johnston, C.L., Diekmann, D. and Hall, A. (1992). The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell, 70, 401-410   DOI   ScienceOn
2 Sun, Y., Ling, K., Wagoner, M.P. and Anderson, R.A. (2007). Type I gamma phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration. J. Cell Biol., 178, 297-308   DOI   ScienceOn
3 Tadokoro, S., Shattil, S.J., Eto, K., Tai, V., Liddington, R.C., de Pereda, J.M., Ginsberg, M.H. and Calderwood, D.A. (2003): Talin binding to integrin beta tails: a final common step in integrin activation. Science, 302, 103-106   DOI   ScienceOn
4 Takei, K. and Haucke, V. (2001). Clathrin-mediated endocytosis: membrane factors pull the trigger. Trends Cell Biol., 11, 385-391   DOI   ScienceOn
5 Theard, D., Steiner, M., Kalicharan, D., Hoekstra, D. and van Ijzendoorn, S.C. (2007). Cell polarity development and protein trafficking in hepatocytes lacking E-cadherin/betacatenin-based adherens junctions. Mol. Biol. Cell, 18, 2313-2321   DOI   ScienceOn
6 Vega-Salas, D.E., Salas, P.J., Gundersen, D. and Rodriguez-Boulan, E. (1987). Formation of the apical pole of epithelial (Madin-Darby canine kidney) cells: polarity of an apical protein is independent of tight junctions while segregation of a basolateral marker requires cell-cell interactions. J. Cell Biol., 104, 905-916   DOI
7 Yam, P.T., Wilson, C.A., Ji, L., Hebert, B., Barnhart, E.L., Dye, N.A., Wiseman, P.W., Danuser, G. and Theriot, J.A. (2007). Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J. Cell Biol., 178, 1207-1221   DOI   ScienceOn
8 Zigmond, S.H. (1996). Signal transduction and actin filament organization. Curr. Opin. Cell Biol., 8, 66-73   DOI   ScienceOn
9 Zuppinger, C., Eppenberger-Eberhardt, M. and Eppenberger, H.M. (2000). N-Cadherin: structure, function and importance in the formation of new intercalated disc-like cell contacts in cardiomyocytes. Heart Fail Rev., 5, 251-257   DOI   ScienceOn
10 Arias, A.M. (2001). Epithelial mesenchymal interactions in cancer and development. Cell, 105, 425-431   DOI   ScienceOn
11 Charest, P.G. and Firtel, R.A. (2006). Feedback signaling controls leading-edge formation during chemotaxis. Curr. Opin. Genet. Dev., 16, 339-347   DOI   ScienceOn
12 Brown, M.T., Andrade, J., Radhakrishna, H., Donaldson, J.G., Cooper, J.A. and Randazzo, P.A. (1998). ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src. Mol. Cell. Biol., 18, 7038-7051   DOI
13 Bryant, D.M. and Stow, J.L. (2004). The ins and outs of Ecadherin trafficking. Trends Cell Biol., 14, 427-434   DOI   ScienceOn
14 Cano, A., Perez-Moreno, M.A., Rodrigo, I., Locascio, A., Blanco, M.J., del Barrio, M.G., Portillo, F. and Nieto, M.A. (2000). The transcription factor snail controls epithelialmesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol., 2, 76-83   DOI   ScienceOn
15 Gong, L.W., Di Paolo, G., Diaz, E., Cestra, G., Diaz, M.E., Lindau, M., De Camilli, P. and Toomre, D. (2005). Phosphatidylinositol phosphate kinase type I gamma regulates dynamics of large dense-core vesicle fusion. Proc. Natl. Acad. Sci. USA, 102, 5204-5209
16 Hajra, K.M., Chen, D.Y. and Fearon, E.R. (2002). The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer. Res., 62, 1613-1618
17 Honda, A., Nogami, M., Yokozeki, T., Yamazaki, M., Nakamura, H., Watanabe, H., Kawamoto, K., Nakayama, K., Morris, A.J., Frohman, M.A. and Kanaho, Y. (1999). Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell, 99, 521-532   DOI   ScienceOn
18 Insall, R.H. and Weiner, O.D. (2001). PIP3, PIP2, and cell movement--similar messages, different meanings? Dev. Cell, 1, 743-747   DOI   ScienceOn
19 Ishihara, H., Shibasaki, Y., Kizuki, N., Katagiri, H., Yazaki, Y., Asano, T. and Oka, Y. (1996). Cloning of cDNAs encoding two isoforms of 68-kDa type I phosphatidylinositol-4-phosphate 5-kinase. J. Biol. Chem., 271, 23611-23614   DOI   ScienceOn
20 Ishihara, H., Shibasaki, Y., Kizuki, N., Wada, T., Yazaki, Y., Asano, T. and Oka, Y. (1998). Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family. J. Biol. Chem., 273, 8741-8748   DOI   ScienceOn
21 Itoh, T., Ijuin, T. and Takenawa, T. (1998). A novel phosphatidylinositol-5-phosphate 4-kinase (phosphatidylinositol-phosphate kinase IIgamma) is phosphorylated in the endoplasmic reticulum in response to mitogenic signals. J. Biol. Chem., 273, 20292-20299   DOI   ScienceOn
22 Ling, K., Doughman, R.L., Iyer, V.V., Firestone, A.J., Bairstow, S.F., Mosher, D.F., Schaller, M.D. and Anderson, R.A. (2003). Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate kinase by Src regulates an integrin-talin switch. J. Cell Biol., 163, 1339-1349   DOI   ScienceOn
23 Martin, T.F. (2001). PI(4,5)P(2) regulation of surface membrane traffic. Curr. Opin. Cell Biol., 13, 493-499   DOI   ScienceOn
24 Moss, J. and Vaughan, M. (1998). Molecules in the ARF orbit. J. Biol. Chem., 273, 21431-21434   DOI   ScienceOn
25 Nelson, W.J. and Nusse, R. (2004). Convergence of Wnt, beta-catenin, and cadherin pathways. Science, 303, 1483-1487   DOI   ScienceOn
26 Niggli, V. (2005). Regulation of protein activities by phosphoinositide phosphates. Annu. Rev. Cell Dev. Biol., 21, 57- 79   DOI   ScienceOn
27 Radisky, D.C. (2005). Epithelial-mesenchymal transition. J. Cell Sci., 118, 4325-4326   DOI   ScienceOn
28 Willis, B.C. and Borok, Z. (2007). TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am. J. Physiol. Lung Cell Mol. Physiol., 293, L525-L534   DOI   ScienceOn
29 Downes, C.P., Gray, A. and Lucocq, J.M. (2005). Probing phosphoinositide functions in signaling and membrane trafficking. Trends Cell Biol., 15, 259-268   DOI   ScienceOn
30 Tolias, K.F., Couvillon, A.D., Cantley, L.C. and Carpenter, C.L. (1998). Characterization of a Rac1- and RhoGDI-associated lipid kinase signaling complex. Mol. Cell Biol., 18, 762-770   DOI
31 Zavadil, J. and Bottinger, E.P. (2005). TGF-beta and epithelial-to-mesenchymal transitions. Oncogene, 24, 5764-5774   DOI   ScienceOn
32 Frame, M.C., Fincham, V.J., Carragher, N.O. and Wyke, J.A. (2002). v-Src's hold over actin and cell adhesions. Nat. Rev. Mol. Cell Biol., 3, 233-245   DOI   ScienceOn
33 Horwitz, A.R. and Parsons, J.T. (1999). Cell migration--movin' on. Science, 286, 1102-1103   DOI   ScienceOn
34 D'Souza-Schorey, C. (2005). Disassembling adherens junctions: breaking up is hard to do. Trends Cell Biol., 15, 19-26   DOI   ScienceOn
35 Kirchhausen, T. (1999). Adaptors for clathrin-mediated traffic. Annu. Rev. Cell Dev. Biol., 15, 705-732   DOI   ScienceOn
36 Moustakas, A. and Heldin, C.H. (2007). Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer. Sci., 98, 1512-1520   DOI   ScienceOn
37 Savagner, P. (2001). Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays, 23, 912-923   DOI   ScienceOn
38 Divecha, N., Roefs, M., Halstead, J.R., D'Andrea, S., Fernandez-Borga, M., Oomen, L., Saqib, K.M., Wakelam, M.J. and D'Santos, C. (2000). Interaction of the type Ialpha PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4,5-bisphosphate in the regulation of PLD2 activity. EMBO J., 19, 5440-5449   DOI   ScienceOn
39 Oloumi, A., McPhee, T. and Dedhar, S. (2004). Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim. Biophys. Acta., 1691, 1-15   DOI   ScienceOn
40 Ridley, A.J. and Hall, A. (1992). The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell, 70, 389-399   DOI   ScienceOn
41 Tilghman, R.W., Slack-Davis, J.K., Sergina, N., Martin, K.H., Iwanicki, M., Hershey, E.D., Beggs, H.E., Reichardt, L.F. and Parsons, J.T. (2005). Focal adhesion kinase is required for the spatial organization of the leading edge in migrating cells. J. Cell Sci., 118, 2613-2623   DOI   ScienceOn
42 Wodarz, A. and Nathke, I. (2007). Cell polarity in development and cancer. Nat. Cell Biol., 9, 1016-1024   DOI   ScienceOn
43 Carvell, M.J., Marsh, P.J., Persaud, S.J. and Jones, P.M. (2007). E-Cadherin interactions regulate beta-cell proliferation in islet-like structures. Cell Physiol. Biochem., 20, 617-626   DOI   ScienceOn
44 Frisch, S.M. (1997). The epithelial cell default-phenotype hypothesis and its implications for cancer. Bioessays, 19, 705-709   DOI   ScienceOn
45 Conacci-Sorrell, M., Zhurinsky, J. and Ben-Ze'ev, A. (2002). The cadherin-catenin adhesion system in signaling and cancer. J. Clin. Invest., 109, 987-991   DOI
46 Golub, T. and Caroni, P. (2005). PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility. J. Cell Biol., 169, 151-165   DOI   ScienceOn
47 Hilgemann, D.W. and Ball, R. (1996). Regulation of cardiac Na$^{+}$, Ca$^{2+}$ exchange and KATP potassium channels by PIP2. Science, 273, 956-959   DOI   ScienceOn
48 Donaldson, J.G. and Jackson, C.L. (2000). Regulators and effectors of the ARF GTPases. Curr. Opin. Cell Biol., 12, 475-482   DOI   ScienceOn
49 Anastasiadis, P.Z. and Reynolds, A.B. (2000). The p120 catenin family: complex roles in adhesion, signaling and cancer. J. Cell Sci., 113, 1319-1334
50 Cremona, O. and De Camilli, P. (2001). Phosphoinositides in membrane traffic at the synapse. ., 114, 1041-1052
51 Suh, B.C. and Hille, B. (2005). Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate. Curr. Opin. Neurobiol., 15, 370-378   DOI   ScienceOn
52 Jones, D.R., Sanjuan, M.A. and Merida, I. (2000). Type Ialpha phosphatidylinositol 4-phosphate 5-kinase is a putative target for increased intracellular phosphatidic acid. FEBS Lett., 476, 160-165   DOI   ScienceOn
53 Kam, J.L., Miura, K., Jackson, T.R., Gruschus, J., Roller, P., Stauffer, S., Clark, J., Aneja, R. and Randazzo, P.A. (2000). Phosphoinositide-dependent activation of the ADP-ribosylation factor GTPase-activating protein ASAP1. Evidence for the pleckstrin homology domain functioning as an allosteric site. J. Biol. Chem., 275, 9653-9663   DOI   ScienceOn
54 Oude Weernink, P.A., Schmidt, M. and Jakobs, K.H. (2004). Regulation and cellular roles of phosphoinositide 5-kinases. Eur. J. Pharmacol., 500, 87-99   DOI   ScienceOn
55 Hanahan, D. and Weinberg, R.A. (2000). The hallmarks of cancer. Cell, 100, 57-70   DOI   ScienceOn
56 Thiery, J.P. (2002). Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer., 2, 442-454   DOI   ScienceOn
57 Doughman, R.L., Firestone, A.J., Wojtasiak, M.L., Bunce, M.W. and Anderson, R.A. (2003). Membrane ruffling requires coordination between type Ialpha phosphatidylinositol phosphate kinase and Rac signaling. J. Biol. Chem., 278, 23036-23045   DOI   ScienceOn
58 Kunz, J., Wilson, M.P., Kisseleva, M., Hurley, J.H., Majerus, P.W. and Anderson, R.A. (2000). The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Mol. Cell, 5, 1-11   DOI   ScienceOn
59 Symons, M. (1995). The Rac and Rho pathways as a source of drug targets for Ras-mediated malignancies. Curr. Opin. Biotechnol., 6, 668-674   DOI   ScienceOn
60 Honing, S., Ricotta, D., Krauss, M., Spate, K., Spolaore, B., Motley, A., Robinson, M., Robinson, C., Haucke, V. and Owen, D.J. (2005). Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2. Mol. Cell, 18, 519-531   DOI   ScienceOn
61 Syed, V., Mak, P., Du, C. and Balaji, K.C. (2007). beta-catenin mediates alteration in cell proliferation, motility and invasion of prostate cancer cells by differential expression of E-cadherin and protein kinase D1. J. Cell Biochem., On-line
62 Van Aelst, L. and Symons, M. (2002). Role of Rho family GTPases in epithelial morphogenesis. Genes Dev., 16, 1032-1054   DOI   ScienceOn
63 Vernon, A.E. and LaBonne, C. (2004). Tumor metastasis: a new twist on epithelial-mesenchymal transitions. Curr. Biol., 14, R719-R721   DOI   ScienceOn
64 Yang, S.A., Carpenter, C.L. and Abrams, C.S. (2004). Rho and Rho-kinase mediate thrombin-induced phosphatidylinositol 4-phosphate 5-kinase trafficking in platelets. J. Biol. Chem., 279, 42331-42336   DOI   ScienceOn
65 Janetopoulos, C., Ma, L., Devreotes, P.N. and Iglesias, P.A. (2004). Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton. Proc. Natl. Acad. Sci. USA, 101, 8951-8956
66 DesMarais, V., Ghosh, M., Eddy, R. and Condeelis, J. (2005). Cofilin takes the lead. J. Cell Sci., 118, 19-26   DOI   ScienceOn
67 Jamora, C. and Fuchs, E. (2002). Intercellular adhesion, signalling and the cytoskeleton. Nat. Cell Biol., 4, E101-108   DOI   ScienceOn
68 Lanier, L.M. and Gertler, F.B. (2000). Actin cytoskeleton: thinking globally, actin' locally. Curr. Biol., 10, R655-R657   DOI   ScienceOn
69 Vestweber, D. (2008). VE-Cadherin. The major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Arterioscler. Thromb. Vasc. Biol., 28, 223-232   DOI   ScienceOn
70 Ling, K., Doughman, R.L., Firestone, A.J., Bunce, M.W. and Anderson, R.A. (2002). Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature, 420, 89-93   DOI   ScienceOn
71 Powner, D.J. and Wakelam, M.J. (2002). The regulation of phospholipase D by inositol phospholipids and small GTPases. FEBS Lett., 531, 62-64   DOI   ScienceOn
72 Gan, Y., McGraw, T.E. and Rodriguez-Boulan, E. (2002). The epithelial-specific adaptor AP1B mediates post-endocytic recycling to the basolateral membrane. Nat. Cell Biol., 4, 605-609   DOI
73 Rameh, L.E., Tolias, K.F., Duckworth, B.C. and Cantley, L.C. (1997). A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature, 390, 192-196   DOI   ScienceOn
74 Aikawa, Y. and Martin, T.F. (2003). ARF6 regulates a plasma membrane pool of phosphatidylinositol(4,5)bisphosphate required for regulated exocytosis. J. Cell Biol., 162, 647-659   DOI   ScienceOn
75 Becker, K.F., Rosivatz, E., Blechschmidt, K., Kremmer, E., Sarbia, M. and Hofler, H. (2007). Analysis of the E-cadherin repressor Snail in primary human cancers. Cells Tissues Organs, 185, 204-212   DOI   ScienceOn
76 Di Paolo, G., Pellegrini, L., Letinic, K., Cestra, G., Zoncu, R., Voronov, S., Chang, S., Guo, J., Wenk, M.R. and De Camilli, P. (2002). Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin. Nature, 420, 85-89   DOI   ScienceOn
77 Fawcett, J. and Pawson, T. (2000). Signal transduction. NWASP regulation--the sting in the tail. Science, 290, 725-726   DOI   ScienceOn
78 Van Aelst, L. and D'Souza-Schorey, C. (1997). Rho GTPases and signaling networks. Genes Dev., 11, 2295-2322   DOI   ScienceOn
79 Webb, D.J., Parsons, J.T. and Horwitz, A.F. (2002). Adhesion assembly, disassembly and turnover in migrating cells --over and over and over again. Nat. Cell Biol., 4, E97-E100   DOI   ScienceOn
80 Knust, E. (2000). Control of epithelial cell shape and polarity. Curr. Opin. Genet. Dev., 10, 471-475   DOI   ScienceOn
81 Hynes, R.O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell, 110, 673-687   DOI   ScienceOn
82 Ling, K., Bairstow, S.F., Carbonara, C., Turbin, D.A., Huntsman, D.G. and Anderson, R.A. (2007). Type Igamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin. J. Cell Biol., 176, 343-353   DOI   ScienceOn
83 Martel, V., Racaud-Sultan, C., Dupe, S., Marie, C., Paulhe, F., Galmiche, A., Block, M.R. and Albiges-Rizo, C. (2001). Conformation, localization, and integrin binding of talin depend on its interaction with phosphoinositides. J. Biol. Chem., 276, 21217-21227
84 Birchmeier, W. and Birchmeier, C. (1995). Epithelial-mesenchymal transitions in development and tumor progression. EXS, 74, 1-15
85 Halbleib, J.M. and Nelson, W.J. (2006). Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev., 20, 3199-3214   DOI   ScienceOn
86 Kisseleva, M., Feng, Y., Ward, M., Song, C., Anderson, R.A. and Longmore, G.D. (2005). The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha. Mol. Cell Biol., 25, 3956-3966   DOI   ScienceOn
87 Powner, D.J., Payne, R.M., Pettitt, T.R., Giudici, M.L., Irvine, R.F. and Wakelam, M.J. (2005). Phospholipase D2 stimulates integrin-mediated adhesion via phosphatidylinositol 4-phosphate 5-kinase Igamma b. J. Cell Sci., 118, 2975-2986   DOI   ScienceOn
88 Gumbiner, B.M. (1996). Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell, 84, 345-357   DOI   ScienceOn
89 Le, T.L., Yap, A.S. and Stow, J.L. (1999). Recycling of E-cadherin: a potential mechanism for regulating cadherin dynamics. J. Cell Biol., 146, 219-232   DOI
90 Santarius, M., Lee, C.H. and Anderson, R.A. (2006). Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P$_{2}$ pools. Biochem. J., 398, 1-13   DOI   ScienceOn
91 Ling, K., Schill, N.J., Wagoner, M.P., Sun, Y. and Anderson, R.A. (2006). Movin' on up: the role of PtdIns(4,5)P(2) in cell migration. Trends Cell Biol., 16, 276-284   DOI   ScienceOn
92 Boronenkov, I.V., Loijens, J.C., Umeda, M. and Anderson, R.A. (1998). Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol. Biol. Cell., 9, 3547-3560   DOI
93 Jenkins, G.H., Fisette, P.L. and Anderson, R.A. (1994). Type I phosphatidylinositol 4-phosphate 5-kinase isoforms are specifically stimulated by phosphatidic acid. J. Biol. Chem., 269, 11547-11554
94 Loijens, J.C. and Anderson, R.A. (1996). Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family. J. Biol. Chem., 271, 32937-32943   DOI   ScienceOn
95 Parker, P.J. (1995). Intracellular signalling. PI 3-kinase puts GTP on the Rac. Curr. Biol., 5, 577-579   DOI   ScienceOn
96 Symons, M. (1996), Rho family GTPases: the cytoskeleton and beyond. Trends Biochem. Sci., 21, 178-181   DOI   ScienceOn
97 Wang, F., Herzmark, P., Weiner, O.D., Srinivasan, S., Servant, G. and Bourne, H.R. (2002). Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat. Cell Biol., 4, 513-518   DOI   ScienceOn
98 Hall, A. (1998). Rho GTPases and the actin cytoskeleton. Science, 279, 509-514   DOI   ScienceOn
99 Zhang, X., Loijens, J.C., Boronenkov, I.V., Parker, G.J., Norris, F.A., Chen, J., Thum, O., Prestwich, G.D., Majerus, P.W. and Anderson, R.A. (1997). Phosphatidylinositol-4-phosphate 5-kinase isozymes catalyze the synthesis of 3-phosphate-containing phosphatidylinositol signaling molecules. J. Biol. Chem., 272, 17756-17761   DOI   ScienceOn
100 Hugo, H., Ackland, M.L., Blick, T., Lawrence, M.G., Clements, J.A., Williams, E.D. and Thompson, E.W. (2007). Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J. Cell Physiol., 213, 374-383   DOI   ScienceOn
101 Nobes, C.D. and Hall, A. (1995). Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell, 81, 53-62   DOI   ScienceOn
102 Brett, T.J., Traub, L.M. and Fremont, D.H. (2002). Accessory protein recruitment motifs in clathrin-mediated endocytosis. Structure, 10, 797-809   DOI   ScienceOn
103 Aoyagi, K., Sugaya, T., Umeda, M., Yamamoto, S., Terakawa, S. and Takahashi, M. (2005). The activation of exocytotic sites by the formation of phosphatidylinositol 4,5-bisphosphate microdomains at syntaxin clusters. J. Biol. Chem., 280, 17346-17352   DOI   ScienceOn
104 Bonifacino, J.S. and Traub, L.M. (2003). Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu. Rev. Biochem., 72, 395-447   DOI   ScienceOn