Regulation of chemotaxis by the orchestrated activation of Ras, PI3K, and TOR

European Journal of Cell Biology

Volumn 85, Issue 9-10, 2006, Pages 873-895

  Sasaki, Atsuo T ^a,b   Firtel, Richard A ^a  

^a SECTION OF CELL AND DEVELOPMENTAL BIOLOGY   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Cell polarity; Directional movement; G protein; PI3K; PTEN; Ras; TOR

Indexed keywords

ACTIN; ACTIN RELATED PROTEIN 2; ACTIN RELATED PROTEIN 3; CYTOSKELETON PROTEIN; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOTRANSFERASE; PROTEIN CDC42; PROTEIN KINASE B; PROTEIN P13K; PROTEIN RAS; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; TARGET OF RAPAMYCIN KINASE; UNCLASSIFIED DRUG; WISKOTT ALDRICH SYNDROME PROTEIN;

ARTICLE; CANCER; CELL GROWTH; CELL MIGRATION; CELL MOTILITY; CELL MOTION; CELL POLARITY; CHEMOTAXIS; CYTOSKELETON; DEVELOPMENTAL DISORDER; DICTYOSTELIUM DISCOIDEUM; ENZYME ACTIVATION; FEEDBACK SYSTEM; HUMAN; IMMUNE DEFICIENCY; MAMMAL CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; YEAST;

DICTYOSTELIUM DISCOIDEUM; EUKARYOTA; MAMMALIA;

EID: 33748376922     PISSN: 01719335     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejcb.2006.04.007     Document Type: Article

References (227)

1. Alessi D.R., Andjelkovic M., Caudwell B., Cron P., Morrice N., Cohen P., and Hemmings B.A. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15 (1996) 6541-6551
2. Allen W.E., Zicha D., Ridley A.J., and Jones G.E. A role for Cdc42 in macrophage chemotaxis. J. Cell Biol. 141 (1998) 1147-1157
3. Ambruso D.R., Knall C., Abell A.N., Panepinto J., Kurkchubasche A., Thurman G., Gonzalez-Aller C., Hiester A., deBoer M., Harbeck R.J., Oyer R., Johnson G.L., and Roos D. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc. Natl. Acad. Sci. USA 97 (2000) 4654-4659
4. Anai M., Shojima N., Katagiri H., Ogihara T., Sakoda H., Onishi Y., Ono H., Fujishiro M., Fukushima Y., Horike N., Viana A., Kikuchi M., Noguchi N., Takahashi S., Takata K., Oka Y., Uchijima Y., Kurihara H., and Asano T. A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis. J. Biol. Chem. 280 (2005) 18525-18535
5. Anton I.M., de la Fuente M.A., Sims T.N., Freeman S., Ramesh N., Hartwig J.H., Dustin M.L., and Geha R.S. WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation. Immunity 16 (2002) 193-204
6. Aspenstrom P. The verprolin family of proteins: regulators of cell morphogenesis and endocytosis. FEBS Lett. 579 (2005) 5253-5259
7. Audhya A., Loewith R., Parsons A.B., Gao L., Tabuchi M., Zhou H., Boone C., Hall M.N., and Emr S.D. Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J. 23 (2004) 3747-3757
8. Augsten M., Pusch R., Biskup C., Rennert K., Wittig U., Beyer K., Blume A., Wetzker R., Friedrich K., and Rubio I. Live-cell imaging of endogenous Ras-GTP illustrates predominant Ras activation at the plasma membrane. EMBO Rep. 7 (2006) 46-51
9. Badolato R., Sozzani S., Malacarne F., Bresciani S., Fiorini M., Borsatti A., Albertini A., Mantovani A., Ugazio A.G., and Notarangelo L.D. Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine. J. Immunol. 161 (1998) 1026-1033
10. Baldauf S.L., Roger A.J., Wenk-Siefert I., and Doolittle W.F. A kingdom-level phylogeny of eukaryotes based on combined protein data. Science 290 (2000) 972-977
11. Bear J.E., Rawls J.F., and Saxe III C.L. SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development. J. Cell Biol. 142 (1998) 1325-1335
12. Bivona T.G., Perez De Castro I., Ahearn I.M., Grana T.M., Chiu V.K., Lockyer P.J., Cullen P.J., Pellicer A., Cox A.D., and Philips M.R. Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature 424 (2003) 694-698
13. Biyasheva A., Svitkina T., Kunda P., Baum B., and Borisy G. Cascade pathway of filopodia formation downstream of SCAR. J. Cell Sci. 117 (2004) 837-848
14. Blagg S.L., Stewart M., Sambles C., and Insall R.H. PIR121 regulates pseudopod dynamics and SCAR activity in Dictyostelium. Curr. Biol. 13 (2003) 1480-1487
15. Bompard G., and Caron E. Regulation of WASP/WAVE proteins: making a long story short. J. Cell Biol. 166 (2004) 957-962
16. Brock C., Schaefer M., Reusch H., Czupalla C., Michalke M., Spicher K., Schultz G., and Nurnberg B. Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101 phosphoinositide 3-kinase gamma. J. Cell Biol. 160 (2003) 89-99
17. Byfield M.P., Murray J.T., and Backer J.M. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J. Biol. Chem. 280 (2005) 33076-33082
18. Camps M., Ruckle T., Ji H., Ardissone V., Rintelen F., Shaw J., Ferrandi C., Chabert C., Gillieron C., Francon B., Martin T., Gretener D., Perrin D., Leroy D., Vitte P.A., Hirsch E., Wymann M.P., Cirillo R., Schwarz M.K., and Rommel C. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat. Med. 11 (2005) 936-943
19. Cantley L.C. The phosphoinositide 3-kinase pathway. Science 296 (2002) 1655-1657
20. Cau J., and Hall A. Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways. J. Cell Sci. 118 (2005) 2579-2587
21. Chen M.Y., Long Y., and Devreotes P.N. A novel cytosolic regulator, Pianissimo, is required for chemoattractant receptor and G protein-mediated activation of the 12 transmembrane domain adenylyl cyclase in Dictyostelium. Genes Dev. 11 (1997) 3218-3231
22. Chiu V.K., Bivona T., Hach A., Sajous J.B., Silletti J., Wiener H., Johnson II R.L., Cox A.D., and Philips M.R. Ras signalling on the endoplasmic reticulum and the Golgi. Nat. Cell Biol. 4 (2002) 343-350
23. Chung C.Y., and Firtel R.A. PAKa, a putative PAK family member, is required for cytokinesis and the regulation of the cytoskeleton in Dictyostelium discoideum cells during chemotaxis. J. Cell Biol. 147 (1999) 559-576
24. Chung C.Y., Funamoto S., and Firtel R.A. Signaling pathways controlling cell polarity and chemotaxis. Trends Biochem. Sci. 26 (2001) 557-566
25. Chung C.Y., Potikyan G., and Firtel R.A. Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol. Cell 7 (2001) 937-947
26. Comer F.I., Lippincott C.K., Masbad J.J., and Parent C.A. The PI3K-mediated activation of CRAC independently regulates adenylyl cyclase activation and chemotaxis. Curr. Biol. 15 (2005) 134-139
27. Cory G.O., and Ridley A.J. Cell motility: braking WAVEs. Nature 418 (2002) 732-733
28. Cory G.O., Garg R., Cramer R., and Ridley A.J. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. J. Biol. Chem. 277 (2002) 45115-45121
29. Cote J.F., Motoyama A.B., Bush J.A., and Vuori K. A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling. Nat. Cell Biol. 7 (2005) 797-807
30. Czuchra A., Wu X., Meyer H., van Hengel J., Schroeder T., Geffers R., Rottner K., and Brakebusch C. Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells. Mol. Biol. Cell 16 (2005) 4473-4484
31. Dahl J.P., Wang-Dunlop J., Gonzales C., Goad M.E., Mark R.J., and Kwak S.P. Characterization of the WAVE1 knock-out mouse: implications for CNS development. J. Neurosci. 23 (2003) 3343-3352
32. Das B., Shu X., Day G.J., Han J., Krishna U.M., Falck J.R., and Broek D. Control of intramolecular interactions between the pleckstrin homology and Dbl homology domains of Vav and Sos1 regulates Rac binding. J. Biol. Chem. 275 (2000) 15074-15081
33. Derry J.M., Ochs H.D., and Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell 79 (1994) (following 922)
34. Devreotes P., and Janetopoulos C. Eukaryotic chemotaxis: distinctions between directional sensing and polarization. J. Biol. Chem. 278 (2003) 20445-20448
35. Dong L.Q., and Liu F. PDK2: the missing piece in the receptor tyrosine kinase signaling pathway puzzle. Am. J. Physiol. Endocrinol. Metab. 289 (2005) E187-E196
36. Dong J., and Pan D. Tsc2 is not a critical target of Akt during normal Drosophila development. Genes Dev. 18 (2004) 2479-2484
37. Dong X., Mo Z., Bokoch G., Guo C., Li Z., and Wu D. P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Curr. Biol. 15 (2005) 1874-1879
38. Duchek P., Somogyi K., Jekely G., Beccari S., and Rorth P. Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell 107 (2001) 17-26
39. Eden S., Rohatgi R., Podtelejnikov A.V., Mann M., and Kirschner M.W. Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418 (2002) 790-793
40. Ehrhardt A., Ehrhardt G.R., Guo X., and Schrader J.W. Ras and relatives - job sharing and networking keep an old family together. Exp. Hematol. 30 (2002) 1089-1106
41. Eichinger L., Pachebat J.A., Glockner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R., Loomis W.F., Platzer M., Kay R.R., Williams J., Dear P.H., Noegel A.A., Barrell B., and Kuspa A. The genome of the social amoeba Dictyostelium discoideum. Nature 435 (2005) 43-57
42. Enomoto A., Murakami H., Asai N., Morone N., Watanabe T., Kawai K., Murakumo Y., Usukura J., Kaibuchi K., and Takahashi M. Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev. Cell 9 (2005) 389-402
43. Erickson M.R., Galletta B.J., and Abmayr S.M. Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J. Cell Biol. 138 (1997) 589-603
44. Fadri M., Daquinag A., Wang S., Xue T., and Kunz J. The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol. Biol. Cell 16 (2005) 1883-1900
45. Feng Q., Baird D., and Cerione R.A. Novel regulatory mechanisms for the Dbl family guanine nucleotide exchange factor Cool-2/alpha-Pix. EMBO J. 23 (2004) 3492-3504
46. Fivaz M., and Meyer T. Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin. J. Cell Biol. 170 (2005) 429-441
47. Fleming I.N., Gray A., and Downes C.P. Regulation of the Rac1-specific exchange factor Tiam1 involves both phosphoinositide 3-kinase-dependent and -independent components. Biochem. J. 351 (2000) 173-182
48. Friedl P. Prespecification and plasticity: shifting mechanisms of cell migration. Curr. Opin. Cell Biol. 16 (2004) 14-23
49. Fruman D.A., and Cantley L.C. Phosphoinositide 3-kinase in immunological systems. Semin. Immunol. 14 (2002) 7-18
50. Fukata M., Nakagawa M., and Kaibuchi K. Roles of Rho-family GTPases in cell polarisation and directional migration. Curr. Opin. Cell Biol. 15 (2003) 590-597
51. Fukui Y., Hashimoto O., Sanui T., Oono T., Koga H., Abe M., Inayoshi A., Noda M., Oike M., Shirai T., and Sasazuki T. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature 412 (2001) 826-831
52. Funamoto S., Milan K., Meili R., and Firtel R.A. Role of phosphatidylinositol 3′ kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in dictyostelium. J. Cell Biol. 153 (2001) 795-810
53. Funamoto S., Meili R., Lee S., Parry L., and Firtel R.A. Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 109 (2002) 611-623
54. Gakidis M.A., Cullere X., Olson T., Wilsbacher J.L., Zhang B., Moores S.L., Ley K., Swat W., Mayadas T., and Brugge J.S. Vav GEFs are required for beta2 integrin-dependent functions of neutrophils. J. Cell Biol. 166 (2004) 273-282
55. Gautreau A., Ho H.Y., Li J., Steen H., Gygi S.P., and Kirschner M.W. Purification and architecture of the ubiquitous Wave complex. Proc. Natl. Acad. Sci. USA 101 (2004) 4379-4383
56. Giehl K. Oncogenic Ras in tumour progression and metastasis. Biol. Chem. 386 (2005) 193-205
57. Glogauer M., Marchal C.C., Zhu F., Worku A., Clausen B.E., Foerster I., Marks P., Downey G.P., Dinauer M., and Kwiatkowski D.J. Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions. J. Immunol. 170 (2003) 5652-5657
58. Gomez-Mouton C., Lacalle R.A., Mira E., Jimenez-Baranda S., Barber D.F., Carrera A.C., Martinez A.C., and Manes S. Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J. Cell Biol. 164 (2004) 759-768
59. Goncharova E., Goncharov D., Noonan D., and Krymskaya V.P. TSC2 modulates actin cytoskeleton and focal adhesion through TSC1-binding domain and the Rac1 GTPase. J. Cell Biol. 167 (2004) 1171-1182
60. Grimsley C.M., Kinchen J.M., Tosello-Trampont A.C., Brugnera E., Haney L.B., Lu M., Chen Q., Klingele D., Hengartner M.O., and Ravichandran K.S. Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J. Biol. Chem. 279 (2004) 6087-6097
61. Gu Y., Jia B., Yang F.C., D'Souza M., Harris C.E., Derrow C.W., Zheng Y., and Williams D.A. Biochemical and biological characterization of a human Rac2 GTPase mutant associated with phagocytic immunodeficiency. J. Biol. Chem. 276 (2001) 15929-15938
62. Gu Y., Filippi M.D., Cancelas J.A., Siefring J.E., Williams E.P., Jasti A.C., Harris C.E., Lee A.W., Prabhakar R., Atkinson S.J., Kwiatkowski D.J., and Williams D.A. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 302 (2003) 445-449
63. Guertin D.A., and Sabatini D.M. An expanding role for mTOR in cancer. Trends Mol. Med. 11 (2005) 353-361
64. Han J., Luby-Phelps K., Das B., Shu X., Xia Y., Mosteller R.D., Krishna U.M., Falck J.R., White M.A., and Broek D. Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science 279 (1998) 558-560
65. Hancock J.F. Ras proteins: different signals from different locations. Nat. Rev. Mol. Cell Biol. 4 (2003) 373-384
66. Hannigan M., Zhan L., Li Z., Ai Y., Wu D., and Huang C.K. Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Proc. Natl. Acad. Sci. USA 99 (2002) 3603-3608
67. Hara K., Maruki Y., Long X., Yoshino K., Oshiro N., Hidayat S., Tokunaga C., Avruch J., and Yonezawa K. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110 (2002) 177-189
68. Harada K., Truong A.B., Cai T., and Khavari P.A. The class II phosphoinositide 3-kinase C2beta is not essential for epidermal differentiation. Mol. Cell. Biol. 25 (2005) 11122-11130
69. Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8 (2005) 179-183
70. Heit B., Tavener S., Raharjo E., and Kubes P. An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients. J. Cell Biol. 159 (2002) 91-102
71. Heo W.D., and Meyer T. Switch-of-function mutants based on morphology classification of Ras superfamily small GTPases. Cell 113 (2003) 315-328
72. Higuchi M., Masuyama N., Fukui Y., Suzuki A., and Gotoh Y. Akt mediates Rac/Cdc42-regulated cell motility in growth factor-stimulated cells and in invasive PTEN knockout cells. Curr. Biol. 11 (2001) 1958-1962
73. Hill K., Krugmann S., Andrews S.R., Coadwell W.J., Finan P., Welch H.C., Hawkins P.T., and Stephens L.R. Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits. J. Biol. Chem. 280 (2005) 4166-4173
74. Hirsch E., Katanaev V., Garlanda C., Azzolino O., Pirola L., Silengo L., Sozzani S., Mantovani A., Altruda F., and Wymann M. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287 (2000) 1049-1053
75. Ho H.Y., Rohatgi R., Ma L., and Kirschner M.W. CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family. Proc. Natl. Acad. Sci. USA 98 (2001) 11306-11311
76. Ho H.Y., Rohatgi R., Lebensohn A.M., Le M., Li J., Gygi S.P., and Kirschner M.W. Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex. Cell 118 (2004) 203-216
77. Ho H.L., Shiau Y.S., and Chen M.Y. Saccharomyces cerevisiae TSC11/AVO3 participates in regulating cell integrity and functionally interacts with components of the Tor2 complex. Curr. Genet. 47 (2005) 273-288
78. Holz M.K., Ballif B.A., Gygi S.P., and Blenis J. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 123 (2005) 569-580
79. Hresko R.C., and Mueckler M. mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. J. Biol. Chem. 280 (2005) 40406-40416
80. Huang Y.E., Iijima M., Parent C.A., Funamoto S., Firtel R.A., and Devreotes P. Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P3 to the leading edge of chemotaxing cells. Mol. Biol. Cell 14 (2003) 1913-1922
81. Ibarra N., Pollitt A., and Insall R.H. Regulation of actin assembly by SCAR/WAVE proteins. Biochem. Soc. Trans. 33 (2005) 1243-1246
82. Iijima M., and Devreotes P. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109 (2002) 599-610
83. Iijima M., Huang Y.E., and Devreotes P. Temporal and spatial regulation of chemotaxis. Dev. Cell 3 (2002) 469-478
84. Innocenti M., Zucconi A., Disanza A., Frittoli E., Areces L.B., Steffen A., Stradal T.E., Di Fiore P.P., Carlier M.F., and Scita G. Abi1 is essential for the formation and activation of a WAVE2 signalling complex. Nat. Cell Biol. 6 (2004) 319-327
85. Insall R.H., Borleis J., and Devreotes P.N. The aimless RasGEF is required for processing of chemotactic signals through G-protein-coupled receptors in Dictyostelium. Curr. Biol. 6 (1996) 719-729
86. Irie H.Y., Pearline R.V., Grueneberg D., Hsia M., Ravichandran P., Kothari N., Natesan S., and Brugge J.S. Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. J. Cell Biol. 171 (2005) 1023-1034
87. Itoh R.E., Kurokawa K., Ohba Y., Yoshizaki H., Mochizuki N., and Matsuda M. Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol. Cell. Biol. 22 (2002) 6582-6591
88. Jacinto E., Loewith R., Schmidt A., Lin S., Ruegg M.A., Hall A., and Hall M.N. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat. Cell Biol. 6 (2004) 1122-1128
89. Janetopoulos C., Jin T., and Devreotes P. Receptor-mediated activation of heterotrimeric G-proteins in living cells. Science 291 (2001) 2408-2411
90. Janetopoulos C., Ma L., Devreotes P.N., and Iglesias P.A. Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton. Proc. Natl. Acad. Sci. USA 101 (2004) 8951-8956
91. Janmey P.A., and Lindberg U. Cytoskeletal regulation: rich in lipids. Nat. Rev. Mol. Cell Biol. 5 (2004) 658-666
92. Jin T., Zhang N., Long Y., Parent C.A., and Devreotes P.N. Localization of the G protein betagamma complex in living cells during chemotaxis. Science 287 (2000) 1034-1036
93. Kae H., Lim C.J., Spiegelman G.B., and Weeks G. Chemoattractant-induced Ras activation during Dictyostelium aggregation. EMBO Rep. 5 (2004) 602-606
94. Kaeberlein M., Powers III R.W., Steffen K.K., Westman E.A., Hu D., Dang N., Kerr E.O., Kirkland K.T., Fields S., and Kennedy B.K. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310 (2005) 1193-1196
95. Kato M., Miki H., Kurita S., Endo T., Nakagawa H., Miyamoto S., and Takenawa T. WICH, a novel verprolin homology domain-containing protein that functions cooperatively with N-WASP in actin-microspike formation. Biochem. Biophys. Res. Commun. 291 (2002) 41-47
96. Katso R., Okkenhaug K., Ahmadi K., White S., Timms J., and Waterfield M.D. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu. Rev. Cell Dev. Biol. 17 (2001) 615-675
97. Katzav S., Martin-Zanca D., and Barbacid M. vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells. EMBO J. 8 (1989) 2283-2290
98. Kheir W.A., Gevrey J.C., Yamaguchi H., Isaac B., and Cox D. A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages. J. Cell Sci. 118 (2005) 5369-5379
99. Khosla M., Spiegelman G.B., Insall R., and Weeks G. Functional overlap of the Dictyostelium RasG, RasD and RasB proteins. J. Cell Sci. 113 (2000) 1427-1434
100. Kim D.H., Sarbassov D.D., Ali S.M., King J.E., Latek R.R., Erdjument-Bromage H., Tempst P., and Sabatini D.M. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110 (2002) 163-175
101. Klionsky D.J. The molecular machinery of autophagy: unanswered questions. J. Cell Sci. 118 (2005) 7-18
102. Kobayashi S., Shirai T., Kiyokawa E., Mochizuki N., Matsuda M., and Fukui Y. Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3. Biochem. J. 354 (2001) 73-78
103. Kraynov V.S., Chamberlain C., Bokoch G.M., Schwartz M.A., Slabaugh S., and Hahn K.M. Localized Rac activation dynamics visualized in living cells. Science 290 (2000) 333-337
104. Kunda P., Craig G., Dominguez V., and Baum B. Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions. Curr. Biol. 13 (2003) 1867-1875
105. Lauffenburger D.A., and Horwitz A.F. Cell migration: a physically integrated molecular process. Cell 84 (1996) 359-369
106. Lee S., Parent C.A., Insall R., and Firtel R.A. A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium. Mol. Biol. Cell 10 (1999) 2829-2845
107. Lee S., Comer F.I., Sasaki A., McLeod I.X., Duong Y., Okumura K., Yates III J.R., Parent C.A., and Firtel R.A. TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium. Mol. Biol. Cell 16 (2005) 4572-4583
108. Leng Y., Zhang J., Badour K., Arpaia E., Freeman S., Cheung P., Siu M., and Siminovitch K. Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation. Proc. Natl. Acad. Sci. USA 102 (2005) 1098-1103
109. Li Z., Jiang H., Xie W., Zhang Z., Smrcka A., and Wu D. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction. Science 287 (2000) 1046-1049
110. Li S., Yamauchi A., Marchal C.C., Molitoris J.K., Quilliam L.A., and Dinauer M.C. Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions. J. Immunol. 169 (2002) 5043-5051
111. Li Z., Hannigan M., Mo Z., Liu B., Lu W., Wu Y., Smrcka A.V., Wu G., Li L., Liu M., Huang C.K., and Wu D. Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42. Cell 114 (2003) 215-227
112. Li Z., Dong X., Wang Z., Liu W., Deng N., Ding Y., Tang L., Hla T., Zeng R., Li L., and Wu D. Regulation of PTEN by Rho small GTPases. Nat. Cell Biol. 7 (2005) 399-404
113. Loewith R., Jacinto E., Wullschleger S., Lorberg A., Crespo J.L., Bonenfant D., Oppliger W., Jenoe P., and Hall M.N. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10 (2002) 457-468
114. Lommel S., Benesch S., Rottner K., Franz T., Wehland J., and Kuhn R. Actin pedestal formation by enteropathogenic Escherichia coli and intracellular motility of Shigella flexneri are abolished in N-WASP-defective cells. EMBO Rep. 2 (2001) 850-857
115. Luo J., Manning B.D., and Cantley L.C. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4 (2003) 257-262
116. Ma L., Chen Z., Erdjument-Bromage H., Tempst P., and Pandolfi P.P. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 121 (2005) 179-193
117. Malumbres M., and Barbacid M. RAS oncogenes: the first 30 years. Nat. Rev. Cancer 3 (2003) 459-465
118. Manning B.D., and Cantley L.C. United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling. Biochem. Soc. Trans. 31 (2003) 573-578
119. Manser E., Loo T.H., Koh C.G., Zhao Z.S., Chen X.Q., Tan L., Tan I., Leung T., and Lim L. PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Mol. Cell 1 (1998) 183-192
120. Martin D.E., and Hall M.N. The expanding TOR signaling network. Curr. Opin. Cell Biol. 17 (2005) 158-166
121. Meili R., Ellsworth C., Lee S., Reddy T.B., Ma H., and Firtel R.A. Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium. EMBO J. 18 (1999) 2092-2105
122. Meili R., Ellsworth C., and Firtel R.A. A novel Akt/PKB-related kinase is essential for morphogenesis in Dictyostelium. Curr. Biol. 10 (2000) 708-717
123. Meili R., Sasaki A.T., and Firtel R.A. Rho Rocks PTEN. Nat. Cell Biol. 7 (2005) 334-335
124. Meller N., Irani-Tehrani M., Kiosses W.B., Del Pozo M.A., and Schwartz M.A. Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nat. Cell Biol. 4 (2002) 639-647
125. Meller N., Merlot S., and Guda C. CZH proteins: a new family of Rho-GEFs. J. Cell Sci. 118 (2005) 4937-4946
126. Merlot S., and Firtel R.A. Leading the way: Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J. Cell Sci. 116 (2003) 3471-3478
127. Michaelson D., Silletti J., Murphy G., D'Eustachio P., Rush M., and Philips M.R. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J. Cell Biol. 152 (2001) 111-126
128. Miki H., Fukuda M., Nishida E., and Takenawa T. Phosphorylation of WAVE downstream of mitogen-activated protein kinase signaling. J. Biol. Chem. 274 (1999) 27605-27609
129. Millan J., and Ridley A.J. Rho GTPases and leucocyte-induced endothelial remodelling. Biochem. J. 385 (2005) 329-337
130. Mochizuki N., Yamashita S., Kurokawa K., Ohba Y., Nagai T., Miyawaki A., and Matsuda M. Spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Nature 411 (2001) 1065-1068
131. Moon S.Y., and Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol. 13 (2003) 13-22
132. Mullins R.D., Stafford W.F., and Pollard T.D. Structure, subunit topology, and actin-binding activity of the Arp2/3 complex from Acanthamoeba. J. Cell Biol. 136 (1997) 331-343
133. Murakoshi H., Iino R., Kobayashi T., Fujiwara T., Ohshima C., Yoshimura A., and Kusumi A. Single-molecule imaging analysis of Ras activation in living cells. Proc. Natl. Acad. Sci. USA 101 (2004) 7317-7322
134. Myers S.A., Han J.W., Lee Y., Firtel R.A., and Chung C.Y. A Dictyostelium homologue of WASP is required for polarized F-actin assembly during chemotaxis. Mol. Biol. Cell 16 (2005) 2191-2206
135. Nishihara H., Kobayashi S., Hashimoto Y., Ohba F., Mochizuki N., Kurata T., Nagashima K., and Matsuda M. Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins. Biochim. Biophys. Acta 1452 (1999) 179-187
136. Nobes C.D., and Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81 (1995) 53-62
137. Nobukuni T., Joaquin M., Roccio M., Dann S.G., Kim S.Y., Gulati P., Byfield M.P., Backer J.M., Natt F., Bos J.L., Zwartkruis F.J., and Thomas G. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc. Natl. Acad. Sci. USA 102 (2005) 14238-14243
138. Nombela-Arrieta C., Lacalle R.A., Montoya M.C., Kunisaki Y., Megias D., Marques M., Carrera A.C., Manes S., Fukui Y., Martinez A.C., and Stein J.V. Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Immunity 21 (2004) 429-441
139. Nozumi M., Nakagawa H., Miki H., Takenawa T., and Miyamoto S. Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone. J. Cell Sci. 116 (2003) 239-246
140. Obermeier A., Ahmed S., Manser E., Yen S.C., Hall C., and Lim L. PAK promotes morphological changes by acting upstream of Rac. EMBO J. 17 (1998) 4328-4339
141. Odorizzi G., Babst M., and Emr S.D. Phosphoinositide signaling and the regulation of membrane trafficking in yeast. Trends Biochem. Sci. 25 (2000) 229-235
142. Oikawa T., Yamaguchi H., Itoh T., Kato M., Ijuin T., Yamazaki D., Suetsugu S., and Takenawa T. PtdIns(3,4,5)P3 binding is necessary for WAVE2-induced formation of lamellipodia. Nat. Cell Biol. 6 (2004) 420-426
143. Okudela K., Hayashi H., Ito T., Yazawa T., Suzuki T., Nakane Y., Sato H., Ishi H., KeQin X., Masuda A., Takahashi T., and Kitamura H. K-ras gene mutation enhances motility of immortalized airway cells and lung adenocarcinoma cells via Akt activation: possible contribution to non-invasive expansion of lung adenocarcinoma. Am. J. Pathol. 164 (2004) 91-100
144. Olofsson B. Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell Signal. 11 (1999) 545-554
145. Pacold M., Suire S., Perisic O., Lara-Gonzalez S., Davis C., Walker E., Hawkins P., Stephens L., Eccleston J., and Williams R. Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma. Cell 103 (2000) 931-943
146. Panchal S.C., Kaiser D.A., Torres E., Pollard T.D., and Rosen M.K. A conserved amphipathic helix in WASP/Scar proteins is essential for activation of Arp2/3 complex. Nat. Struct. Biol. 10 (2003) 591-598
147. Parent C.A. Making all the right moves: chemotaxis in neutrophils and Dictyostelium. Curr. Opin. Cell Biol. 16 (2004) 4-13
148. Parent C.A., and Devreotes P.N. A cell's sense of direction. Science 284 (1999) 765-770
149. Park K.C., Rivero F., Meili R., Lee S., Apone F., and Firtel R.A. Rac regulation of chemotaxis and morphogenesis in Dictyostelium. EMBO J. 23 (2004) 4177-4189
150. Peck J., Douglas G.T., Wu C.H., and Burbelo P.D. Human RhoGAP domain-containing proteins: structure, function and evolutionary relationships. FEBS Lett. 528 (2002) 27-34
151. Perez de Castro I., Bivona T.G., Philips M.R., and Pellicer A. Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus. Mol. Cell. Biol. 24 (2004) 3485-3496
152. Pollard T.D., and Borisy G.G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112 (2003) 453-465
153. Pollock C.B., Shirasawa S., Sasazuki T., Kolch W., and Dhillon A.S. Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells. Cancer Res. 65 (2005) 1244-1250
154. Postma M., and Van Haastert P.J. A diffusion-translocation model for gradient sensing by chemotactic cells. Biophys. J. 81 (2001) 1314-1323
155. Postma M., Roelofs J., Goedhart J., Gadella T.W., Visser A.J., and Van Haastert P.J. Uniform cAMP stimulation of Dictyostelium cells induces localized patches of signal transduction and pseudopodia. Mol. Biol. Cell 14 (2003) 5019-5027
156. Raftopoulou M., and Hall A. Cell migration: Rho GTPases lead the way. Dev. Biol. 265 (2004) 23-32
157. Ramesh N., Anton I.M., Hartwig J.H., and Geha R.S. WIP, a protein associated with Wiskott-Aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. Proc. Natl. Acad. Sci. USA 94 (1997) 14671-14676
158. Rane M.J., Gozal D., Butt W., Gozal E., Pierce Jr. W.M., Guo S.Z., Wu R., Goldbart A.D., Thongboonkerd V., McLeish K.R., and Klein J.B. Gamma-amino butyric acid type B receptors stimulate neutrophil chemotaxis during ischemia-reperfusion. J. Immunol. 174 (2005) 7242-7249
159. Reif K., and Cyster J. The CDM protein DOCK2 in lymphocyte migration. Trends Cell Biol. 12 (2002) 368-373
160. Repasky G.A., Chenette E.J., and Der C.J. Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis?. Trends Cell Biol. 14 (2004) 639-647
161. Ridley A.J. Rho family proteins: coordinating cell responses. Trends Cell Biol. 11 (2001) 471-477
162. Ridley A.J., and Hall A. The small GTP-binding protein rho regulates the
163. Ridley A.J., Comoglio P.M., and Hall A. Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and Rho in MDCK cells. Mol. Cell. Biol. 15 (1995) 1110-1122
164. Ridley A.J., Schwartz M.A., Burridge K., Firtel R.A., Ginsberg M.H., Borisy G., Parsons J.T., and Horwitz A.R. Cell migration: integrating signals from front to back. Science 302 (2003) 1704-1709
165. Rivero F., and Somesh B.P. Signal transduction pathways regulated by Rho GTPases in Dictyostelium. J. Muscle Res. Cell Motil. 23 (2002) 737-749
166. Rodriguez-Viciana P., Warne P.H., Khwaja A., Marte B.M., Pappin D., Das P., Waterfield M.D., Ridley A., and Downward J. Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras. Cell 89 (1997) 457-467
167. Sanui T., Inayoshi A., Noda M., Iwata E., Stein J.V., Sasazuki T., and Fukui Y. DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. Blood 102 (2003) 2948-2950
168. Sarbassov D.D., Ali S.M., Kim D.H., Guertin D.A., Latek R.R., Erdjument-Bromage H., Tempst P., and Sabatini D.M. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 14 (2004) 1296-1302
169. Sarbassov D.D., Ali S.M., and Sabatini D.M. Growing roles for the mTOR pathway. Curr. Opin. Cell Biol. 17 (2005) 596-603
170. Sarbassov D.D., Guertin D.A., Ali S.M., and Sabatini D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307 (2005) 1098-1101
171. Sasaki A.T., and Firtel R.A. Finding the way: directional sensing and cell polarization through Ras signalling. Novartis Found. Symp. 269 (2005) 73-87 (discussion 87-91, 223-230)
172. Sasaki T., Irie-Sasaki J., Jones R.G., Oliveira-dos-Santos A.J., Stanford W.L., Bolon B., Wakeham A., Itie A., Bouchard D., Kozieradzki I., Joza N., Mak T.W., Ohashi P.S., Suzuki A., and Penninger J.M. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science 287 (2000) 1040-1046
173. Sasaki A.T., Chun C., Takeda K., and Firtel R.A. Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement. J. Cell Biol. 167 (2004) 505-518
174. Scheid M.P., Marignani P.A., and Woodgett J.R. Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B. Mol. Cell. Biol. 22 (2002) 6247-6260
175. Schmidt A., and Hall A. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 16 (2002) 1587-1609
176. Schmidt A., Kunz J., and Hall M.N. TOR2 is required for organization of the actin cytoskeleton in yeast. Proc. Natl. Acad. Sci. USA 93 (1996) 13780-13785
177. Schmidt A., Bickle M., Beck T., and Hall M.N. The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell 88 (1997) 531-542
178. Segarra J., Balenci L., Drenth T., Maina F., and Lamballe F. Combined signaling through ERK, PI3K/AKT and RAC1/p38 is required for met-triggered cortical neuron migration. J. Biol. Chem. 281 (2006) 4771-4778
179. Servant G., Weiner O.D., Neptune E.R., Sedat J.W., and Bourne H.R. Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis. Mol. Biol. Cell 10 (1999) 1163-1178
180. Snapper S.B., Takeshima F., Anton I., Liu C.H., Thomas S.M., Nguyen D., Dudley D., Fraser H., Purich D., Lopez-Ilasaca M., Klein C., Davidson L., Bronson R., Mulligan R.C., Southwick F., Geha R., Goldberg M.B., Rosen F.S., Hartwig J.H., and Alt F.W. N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Nat. Cell Biol. 3 (2001) 897-904
181. Snapper S.B., Meelu P., Nguyen D., Stockton B.M., Bozza P., Alt F.W., Rosen F.S., von Andrian U.H., and Klein C. WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo. J. Leukocyte Biol. 77 (2005) 993-998
182. Srinivasan S., Wang F., Glavas S., Ott A., Hofmann F., Aktories K., Kalman D., and Bourne H.R. Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis. J. Cell Biol. 160 (2003) 375-385
183. Steffen A., Rottner K., Ehinger J., Innocenti M., Scita G., Wehland J., and Stradal T.E. Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J. 23 (2004) 749-759
184. Stephens L., Smrcka A., Cooke F.T., Jackson T.R., Sternweis P.C., and Hawkins P.T. A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein beta gamma subunits. Cell 77 (1994) 83-93
185. Stephens L.R., Eguinoa A., Erdjument-Bromage H., Lui M., Cooke F., Coadwell J., Smrcka A.S., Thelen M., Cadwallader K., Tempst P., and Hawkins P.T. The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101. Cell 89 (1997) 105-114
186. Stovold C.F., Millard T.H., and Machesky L.M. Inclusion of Scar/WAVE3 in a similar complex to Scar/WAVE1 and 2. BMC Cell Biol. 6 (2005) 11
187. Stoyanov B., Volinia S., Hanck T., Rubio I., Loubtchenkov M., Malek D., Stoyanova S., Vanhaesebroeck B., Dhand R., Nurnberg B., et al. Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase. Science 269 (1995) 690-693
188. Stradal T.E., Rottner K., Disanza A., Confalonieri S., Innocenti M., and Scita G. Regulation of actin dynamics by WASP and WAVE family proteins. Trends Cell Biol. 14 (2004) 303-311
189. Suetsugu S., Miki H., and Takenawa T. Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex. Biochem. Biophys. Res. Commun. 260 (1999) 296-302
190. Suetsugu S., Yamazaki D., Kurisu S., and Takenawa T. Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration. Dev. Cell 5 (2003) 595-609
191. Suire S., Coadwell J., Ferguson G.J., Davidson K., Hawkins P., and Stephens L. p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma. Curr. Biol. 15 (2005) 566-570
192. Sukumvanich P., DesMarais V., Sarmiento C.V., Wang Y., Ichetovkin I., Mouneimne G., Almo S., and Condeelis J. Cellular localization of activated N-WASP using a conformation-sensitive antibody. Cell Motil. Cytoskeleton 59 (2004) 141-152
193. Sun C.X., Downey G.P., Zhu F., Koh A.L., Thang H., and Glogauer M. Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass. Blood 104 (2004) 3758-3765
194. Svitkina T.M., and Borisy G.G. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J. Cell Biol. 145 (1999) 1009-1026
195. Szymanski D.B. Breaking the WAVE complex: the point of Arabidopsis trichomes. Curr. Opin. Plant Biol. 8 (2005) 103-112
196. Takenawa T., and Miki H. WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J. Cell Sci. 114 (2001) 1801-1809
197. Thrasher A.J. WASp in immune-system organization and function. Nat. Rev. Immunol. 2 (2002) 635-646
198. Torres E., and Rosen M.K. Protein-tyrosine kinase and GTPase signals cooperate to phosphorylate and activate Wiskott-Aldrich syndrome protein (WASP)/neuronal WASP. J. Biol. Chem. 281 (2006) 3513-3520
199. Tuxworth R.I., Cheetham J.L., Machesky L.M., Spiegelmann G.B., Weeks G., and Insall R.H. Dictyostelium RasG is required for normal motility and cytokinesis, but not growth. J. Cell Biol. 138 (1997) 605-614
200. Vanhaesebroeck B., and Alessi D.R. The PI3K-PDK1 connection: more than just a road to PKB. Biochem. J. 346 (2000) 561-576
201. Vanhaesebroeck B., Ali K., Bilancio A., Geering B., and Foukas L.C. Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem. Sci. 30 (2005) 194-204
202. Vedham V., Phee H., and Coggeshall K.M. Vav activation and function as a rac guanine nucleotide exchange factor in macrophage colony-stimulating factor-induced macrophage chemotaxis. Mol. Cell. Biol. 25 (2005) 4211-4220
203. Vivanco I., and Sawyers C.L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer 2 (2002) 489-501
204. Volinia S., Dhand R., Vanhaesebroeck B., MacDougall L.K., Stein R., Zvelebil M.J., Domin J., Panaretou C., and Waterfield M.D. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J. 14 (1995) 3339-3348
205. Volkman B.F., Prehoda K.E., Scott J.A., Peterson F.C., and Lim W.A. Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich Syndrome. Cell 111 (2002) 565-576
206. Walmsley M.J., Ooi S.K., Reynolds L.F., Smith S.H., Ruf S., Mathiot A., Vanes L., Williams D.A., Cancro M.P., and Tybulewicz V.L. Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling. Science 302 (2003) 459-462
207. Wang F., Herzmark P., Weiner O.D., Srinivasan S., Servant G., and Bourne H.R. Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat. Cell Biol. 4 (2002) 513-518
208. Ward S.G., and Finan P. Isoform-specific phosphoinositide 3-kinase inhibitors as therapeutic agents. Curr. Opin. Pharmacol. 3 (2003) 426-434
209. Watanabe T., Noritake J., and Kaibuchi K. Regulation of microtubules in cell migration. Trends Cell Biol. 15 (2005) 76-83
210. Weiner O.D., Neilsen P.O., Prestwich G.D., Kirschner M.W., Cantley L.C., and Bourne H.R. A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity. Nat. Cell Biol. 4 (2002) 509-513
211. Welch M.D., DePace A.H., Verma S., Iwamatsu A., and Mitchison T.J. The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. J. Cell Biol. 138 (1997) 375-384
212. Welch H.C., Coadwell W.J., Ellson C.D., Ferguson G.J., Andrews S.R., Erdjument-Bromage H., Tempst P., Hawkins P.T., and Stephens L.R. P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac. Cell 108 (2002) 809-821
213. Welch H.C., Condliffe A.M., Milne L.J., Ferguson G.J., Hill K., Webb L.M., Okkenhaug K., Coadwell W.J., Andrews S.R., Thelen M., Jones G.E., Hawkins P.T., and Stephens L.R. P-Rex1 regulates neutrophil function. Curr. Biol. 15 (2005) 1867-1873
214. Whetton A.D., Lu Y., Pierce A., Carney L., and Spooncer E. Lysophospholipids synergistically promote primitive hematopoietic cell chemotaxis via a mechanism involving Vav 1. Blood 102 (2003) 2798-2802
215. Wilkins A., Khosla M., Fraser D.J., Spiegelman G.B., Fisher P.R., Weeks G., and Insall R.H. Dictyostelium RasD is required for normal phototaxis, but not differentiation. Genes Dev. 14 (2000) 1407-1413
216. Worthylake R.A., and Burridge K. RhoA and ROCK promote migration by limiting membrane protrusions. J. Biol. Chem. 278 (2003) 13578-13584
217. Wu Y.C., and Horvitz H.R. C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392 (1998) 501-504
218. Wurmser A.E., and Emr S.D. Novel PtdIns(3)P-binding protein Etf1 functions as an effector of the Vps34 PtdIns 3-kinase in autophagy. J. Cell Biol. 158 (2002) 761-772
219. Xiao Z., Zhang N., Murphy D.B., and Devreotes P.N. Dynamic distribution of chemoattractant receptors in living cells during chemotaxis and persistent stimulation. J. Cell Biol. 139 (1997) 365-374
220. Xu J., Wang F., Van Keymeulen A., Herzmark P., Straight A., Kelly K., Takuwa Y., Sugimoto N., Mitchison T., and Bourne H.R. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114 (2003) 201-214
221. Xu J., Wang F., Van Keymeulen A., Rentel M., and Bourne H.R. Neutrophil microtubules suppress polarity and enhance directional migration. Proc. Natl. Acad. Sci. USA 102 (2005) 6884-6889
222. Yamazaki D., Suetsugu S., Miki H., Kataoka Y., Nishikawa S., Fujiwara T., Yoshida N., and Takenawa T. WAVE2 is required for directed cell migration and cardiovascular development. Nature 424 (2003) 452-456
223. Yan C., Martinez-Quiles N., Eden S., Shibata T., Takeshima F., Shinkura R., Fujiwara Y., Bronson R., Snapper S.B., Kirschner M.W., Geha R., Rosen F.S., and Alt F.W. WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. EMBO J. 22 (2003) 3602-3612
224. Zhang B., Cao H., and Rao G.N. 15(S)-hydroxyeicosatetraenoic acid induces angiogenesis via activation of PI3K-Akt-mTOR-S6K1 signaling. Cancer Res. 65 (2005) 7283-7291
225. Zhou Z., Caron E., Hartwieg E., Hall A., and Horvitz H.R. The C. elegans PH domain protein CED-12 regulates cytoskeletal reorganization via a Rho/Rac GTPase signaling pathway. Dev. Cell 1 (2001) 477-489
226. Zicha D., Allen W.E., Brickell P.M., Kinnon C., Dunn G.A., Jones G.E., and Thrasher A.J. Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome. Br. J. Haematol. 101 (1998) 659-665
227. Zipfel P.A., Bunnell S.C., Witherow D.S., Gu J.J., Chislock E.M., Ring C., and Pendergast A.M. Role for the abi/wave protein complex in T cell receptor-mediated proliferation and cytoskeletal remodeling. Curr. Biol. 16 (2006) 35-46