Phosphoinositide 3-kinases in cell migration

Biology of the Cell

Volumn 101, Issue 1, 2009, Pages 13-29

  Cain, Robert J ^a   Ridley, Anne J ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Actin cytoskeleton; Cell migration; Phosphoinositide; Phosphoinositide 3 kinase (P13K); Rho GTPase; Signalling

Indexed keywords

ISOENZYME; LIPID; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN;

CELL ADHESION; CELL MIGRATION; CELL TYPE; NONHUMAN; POLARIZATION; PRIORITY JOURNAL; PROTEIN LIPID INTERACTION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; STIMULUS; ANIMAL; CELL MOTION; CELL POLARITY; HUMAN; PHYSIOLOGY;

ANIMALIA;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; CELL MOVEMENT; CELL POLARITY; HUMANS; SIGNAL TRANSDUCTION;

EID: 58149395054     PISSN: 02484900     EISSN: 1768322X     Source Type: Journal    
DOI: 10.1042/BC20080079     Document Type: Review

References (166)

1. Ali, K., Bilancio, A., Thomas, M., Pearce, W., Gilfillan, A.M., Tkaczyk, C., Kuehn, N., Gray, A., Giddings, J., Peskett, E., Fox, R., Bruce, I., Walker, C., Sawyer, C. Okkenhaug, K, FInan, P. and Vanhaesebroeck, B. (2004) Essential role for the p110δ phosphoinositide 3-kinase in the allergic response. Nature 431, 1007-1011
2. Amin, M.A., Haas, C.S., Zhu, K., Mansfield, P.J., Kim, M.J., Lackowski, N.P. and Koch, A.E. (2006) Migration Inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, P13 kinase, and NFkB. Blood 107, 2252-2261
3. Andrade, R.M., Wessendarp, M., Gubbels, M.J., Stripen, B. and Subauste, C.S. (2006) CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes. J. Clin. Invest. 118, 2366-2377
4. Backer, J.M. (2008) The regulation and function of Class III P13Ks: novel roles for Vps34. Biochem. J. 410, 1-17
5. Barreiro, O., Yanez-Mo, M., Serrador, J.M., Montoya, M.C., Vicente-Manzanares, M., Tejedor, R., Furthmayr, H. and Sanchez-Madrid, F. (2002) Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J. Cell Biol. 157, 1233-1245
6. Bernard, O. (2007) Lim kinases, regulators of actin dynamics. Int. J. Biochem. Cell Biol. 39, 1071-1076
7. Bernards, A. (2003) GAPs galorel A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila. Biochim. Biophys. Acta 1603, 47-82
8. Bi, L., Okabe, I., Bernard, D.J., Wynshaw-Bods, A. and Nussbaum, R.L. (1999) Proliferative defeat and embryonic lethality in mice homozygous for a deletion in the p110α subunit of phosphoinositide 3-kinase. J. Biol. Chem. 274, 10963-10968
9. Bi, L., Okabe, I., Bernard, D.J. and Nussbaum, R.L. (2002) Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase. Mamm. Genome 13, 169-172
10. Bilancio, A., Okkenhaug, K., Camps, M., Emery, J.L., Ruckle, T., Rommel, C. and Vanhaesebroeck, B. (2006) Key role of the p110δ isoform of P13K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with pl10δ function in B cells. Blood 107, 642-650
11. Blaser, H., Reichman-Fried, M., Castanon, I., Dumstrei, K., Marlow, F.L., Kawakami, K., Solnica-Krezel, L., Heisenberg, C.P. and Raz, E. (2006) Migration of zebrafish primordial germ cells: a role for myosin contraction and cytoplasmic flow. Dev. Cell 11, 613-627
12. 3-Integrin represents an endogenous braking mechanism during neutrophil transmatrix migration. Blood 97, 3251-3258
13. Butcher, E.C. (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67, 1033-1036
14. Carman, C.V. and Springer, T.A. (2004) A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J. Cell Biol. 167, 377-388
15. Carman, C.V., Jun, C.D., Salas, A. and Springer, T.A. (2003) Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1. J. Immunol. 171, 6135-6144
16. Chamberlain, M.D., Berry, T.R., Pastor, M.C. and Anderson, D.H. (2004) The p85α subunit of phosphatidylinositol 3′-kinase binds to and stimulates the GTPase activity of Rab proteins. J. Biol. Chem. 279, 48607-48614
17. Chhabra, E.S. and Higgs, H.N. (2007) The many faces of actin: matching assembly factors with cellular structures. Nat. Cell Biol. 9, 1110-1121
18. Clayton, E., Bardi, G., Bell, S.E., Chantry, D., Downes, C.R, Gray, A., Humphries, L.A, Rawlings, D., Reynolds, H., Vigorito, E. and Turner, M. (2002) A crucial role for the p110δ subunit of phosphatidylinositol 3-kinase in B cell development and activation. J. Exp. Med. 196, 753-763
19. Constantin, G., Majeed, M., Giaguill, C., Piccio, L., Kim, J.Y., Butcher, E.C. and Laudanna, C. (2000) Chemokines trigger immediate β2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity 13, 759-769
20. Costa, C., Barbeds, L., Ambrogio, C., Manazza, A.D., Patrucco, E., Azzolino, O., Neilsen, P.O., Ciraolo, E., Altruda, F., Prestwich, G.D., Chiarle, R., Wymann, M., Ridley, A. and Hirsch, E. (2007) Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinasey γ. Proc. Natl. Acad. Sci. U.S.A. 104, 14354-14359
21. Costello, P.S., Gallagher, M. and Cantrell, D.A. (2002) Sustained and dynamic inosital lipid metabolism inside and outside the immunological synapse. Nat. Immunol. 3, 1082-1089
22. Cote, J.F. and Vuod, K. (2007) GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. Trends Cell Biol. 17, 383-393
23. Cronshaw, D.G., Owen, C., Brown, Z. and Ward, S.G. (2004) Activation of phosphoinositide 3-kinases by the CCR4 ligand macrophage-derived chemokine is a dispensable signal for T lymphocyte chemotaxis. J. Immunol. 172, 7761-7770
24. Czauderna, F, Fechtner, M., Aygün, H., Arnold, W., Klippel, A., Giese, K. and Kaufmann, J. (2003) Functional studies of the PI(3)-kinase signalling pathway employing synthetic and expressed siRNA. Nucleic Acids Res. 31, 670-682
25. DerMardirossian, C. and Bokoch, G.M. (2005) GDIs: central regulatory molecules in Rho GTPase activation. Trends Call Blol. 15, 356-363
26. Domin, J., Pages, F., Volinia, S., Rittenhouse, S.E., Zvelebil, M.J., Stein, R.C. and Waterfield, M.D. (1997) Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin. Biochem. J. 326, 139-147
27. Domin, J., Harper, L., Aubyn, D., Wheeler, M., Florey, O., Haskard, D., Yuan, M. and Zicha, D. (2005) The class II phosphoinositicle 3-ldnase P13K-C2β regulates cell migration by a PtdIns3P dependent mechanism. J. Cell. Physiol. 205, 452-462
28. Dudek, S.M. and Garcia, J.G. (2001) Cytoskeletal regulation of pulmonary vascular permeability. J. Appl. Physiol. 91, 1487-1500
29. Dunn, S.E., Torres, J.V., Oh, J.S., Cylkert, D.M. and Barrett, J.C. (2001) Up-regulation of urokinase-type plasminogen activator by insulin-like growth factor-1 depends upon phosphatidylinositol-3 Idnase and mitogen-activated protein kinase kinase. Cancer Res. 61, 1367-1374
30. Ellerbroek, S.M., Halbleib, J.M., Benavidez, M., Warmka, J.K., Wattenberg, E.V., Stack, M.S. and Hudson, L.G. (2001) Phosphatidylinositol 3-kinase activity in epidermal growth factor-stimulated matrix metalloproteinase-9 production and cell surface association. Cancer Res. 61, 1855-1861
31. Elis, W., Triantafellow, E., Wolters, N.M., Sian, KR., Caponigro, G., Borawski, J., Gaither, L.A., Murphy, L.O., Finan, P.M. and Mackeigan, J.P. (2008) Down-regulation of class 11 phosphoinositide 3-kinase alpha expression below a critical threshold induces apoptotic cell death. Mol. Cancer Res. 6, 614-623
32. Estilo, C.L., O-Charoenrat, P., Ngai, I., Patel, S.G., Reddy, P.G., Dao, S., Shaha, A.R., Kraus, D.H., Boyle, J.O., Wong, R.J., Pfister, D.G., Huryn, J.M., Zlotolow, I.M., Shah, J.R and Singh, B. (2003) The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110α in squamous cell carcinoma of the oral tongue. Clin. Cancer Res. 9, 2300-2306
33. Etienne-Manneville, S. (2004) Cdc42 - the centre of polarity. J. Cell Sci. 117, 1291-1300
34. Etienne-Manneville, S. and Hall, A. (2002) Rho GTPases in cell biology. Nature 420, 629-635
35. Etienne-Manneville, S. and Hall, A. (2003) Cell polarity: Par6, aPKC and cyloskeletal crosstalk. Curr. Opin. Cell Biol. 15, 67-72
36. Etienne-Manneville, S., Manneville, J.B., Nicholls, S., Ferenczi, M.A. and Hall, A. (2005) Cdc42 and Par6-PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization. J. Cell Biol. 170, 895-901
37. Fackler, O.T. and Grosse, R. (2008) Call motility through plasma membrane blabbing. J. Cell Biol. 181, 879-884
38. Fedorov, O., Marsden, B., Pogacic, V., Rellos, P., Muller, S., Bullock, A.N., Schwaller, J., Sundstrom, M. and Knapp, S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A. 104, 20523-20528
39. Fang, D., Nagy, J.A., Pyne, K., Dvorak, H. F. and Dvorak, A.M. (1998) Neutrophils emigrate from venules by a transendotheliall cell pathway in response to FMLP. J. Exp. Med. 187, 903-915
40. Fenteany, G. and Glogauer, M. (2004) Cytoskeletal remodeling in leukocyte function. Curr. Opin. Hematol. 11, 15-24
41. Ferguson, G.J., Milne, L., Kulkami, S., Sasaki, T., Walker, S., Andrews, S., Crabbe, T., Finan, P., Jones, G., Jackson, S., Camps, M., Rommel, C., Wymann, M., Hirsch, E., Hawkins, P. and Stephens, L. (2007) PI(3)Kγ has an important context-dependent role in neutrophill chemokinesis. Nat. Cell Biol. 9, 86-91
42. Ferreira, A.M., Isaacs, H., Hayflick, J.S., Rogers, K.A. and Sandig, M. (2006) The p110δ isoform of P13K differentially regulates β1 and integrin-mediated monocyte adhesion and spreading and modulates diapedesis. Microcirculation 13, 439-456
43. Flevaris, R, Stojanovic, A., Gong, H., Chishti, A., Welch, E. and Du, X. (2007) A molecular switch that controls cell spreading and retraction. J. Cell Biol. 179, 553-565
44. Foster, F.M., Traer, C.J., Abraham, S.M. and Fry, M.J. (2003) The phosphoinositide (PI) 3-kinase family. J. Cell Sci. 116, 3037-3040
45. Friedl, P. (2004) Prespecification and plasticity: shifting mechanisms of cell migration. Curr. Opin. Cell Biol. 16, 14-23
46. Friedl, P. and Brocker, E.B. (2000) The biology of cell locomotion within three-dimensional extracellular matrix. Cell. Mol. Life Sci. 57, 41-64
47. Friedl, P. and Wolf, K. (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat. Rev. Cancer 3, 362-374
48. Friedl, P., Hegerfeldt, Y. and Tusch, M. (2004) Collective cell migration in morphogenesis and cancer. Int. J. Dev. Biol. 48, 441-449
49. Fry, M.J. (2001) Phosphoinositide 3-kinase signalling in breast cancer: how big a role might it play? Breast Cancer Res. 3, 304-312
50. Fulga, T.A. and Rorth, P. (2002) Invasive cell migration is initiated by guided growth of long cellular extensions. Nat. Cell Biol. 4, 715-719
51. Funamoto, S., Milan, K., Meili, R. and Firtel, R.A. (2001) Role of phosphatidylinositol 3′ kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in Dictyostelium. J. Cell Biol. 153, 795-810
52. Funamoto, S., Meili, R., Lee, S., Parry, L. and Firtel, R.A. (2002) Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 109, 611-623
53. Gallo, G. and Letourneau, P. (2002) Axon guidance: proteins turnover in turning growth cones. Curr. Biol. 12, R560-R562
54. Gardiner, E.M., Pestonjamasp, K.N., Bohl, B.P., Chamberlain, C., Hahn, K.M. and Bokoch, G.M. (2002) Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr. Biol. 12, 2029-2034
55. Gavard, J., Lambert, M., Grosheva, I., Marthiens, V., Irinopoulou, T., Riou, J.F., Bershadsky, A. and Mege, R.M. (2004) Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways. J. Cell Sci. 117, 257-270
56. Gerszten, R.E., Friedrich, E.B., Matsui, T., Hung, R.R., Li, L., Force, T. and Rosenzweig, A. (2001) Role of phosphoinositide 3-kinase in monocyte recruitment under flow conditions. J. Biol. Chem. 276, 26846-26851
57. Ginsberg, M.H., Partridge, A. and Shattil, S.J. (2005) Integrin regulation. Curr. Opin. Cell Biol. 17, 509-516
58. Glading, A., Lauffenburger, D.A. and Wells, A. (2002) Cutting to the chase: calpain proteases in cell motility. Trends Cell Biol. 12, 46-54
59. Goldstein, B. and Macara, I.G. (2007) The PAR proteins: fundamental players in animal cell polarization. Dev. Cell 13, 609-622
60. Gonzalez-Mariscal, L., Tapia, R. and Chamorro, D. (2008) Crosstalk of tight junction components with signaling pathways. Biochim. Biophys. Acta 1778, 729-756
61. Govek, E.E., Newey, S.E. and Van Aelst, L. (2005) The role of the Rho GTPases in neuronal development. Genes Dev. 19, 1-49
62. Graupera, M., Guillermet-Guibert, J., Foukas, L.C., Phng, L.K., Cain, R.J., Salpekar, A., Pearce, W., Meek, S., Millan, J., Cutillas, P.R., Smith, A.J., Ridley, A.J., Ruhrberg, C., Gerhardt, H. and Vanhaesebroeck, B. (2008) Angiogenesis selectively requires the p110α isoform of PI3K to control endothelial cell migration. Nature 453, 662-666
63. Grille, S.J., Bellacosa, A., Upson, J., Klein-Szanto, A.J., van Roy, F., Lee-Kwon, W., Donowitz, M., Tsichlis, P.N. and Larue, L. (2003) The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 63, 2172-2178
64. Gupta, T. and Schupbach, T. (2001) Two signals are better than one: border cell migration in Drosophila. Dev. Cell 1, 443-445
65. 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. (1998) Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science 279, 558-560
66. Hannigan, M., Zhan, L., Li, Z., Ai, Y., Wu, D. and Huang, C.K. (2002) Neutrophils lacking phosphoinositide 3-kinase γ show loss of directionality during N-formyl-Met-Lau-Phe-induced chemotaxis. Proc. Natl. Acad. Sci. U.S.A. 99, 3603-3608
67. Harada, K., Truong, A.B., Cai, T. and Khavari, P.A. (2005) The class II phosphoinositide 3-kinase C2β is not essential for epidermal differentiation. Mol. Cell. Biol. 25, 11122-11130
68. Hirsch, E., Katanaev, V.L., Garlanda, C., Azzolino, O., Pirola, L., Silengo, L., Sozzani, S., Mantovani, A., Altruda, F. and Wymann, M.P. (2000) Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation. Science 287, 1049-1053
69. Hoeller, O. and Kay, R.R. (2007) Chemotaxis in the absence of PIP3 gradients. Curr. Biol. 17, 813-817
70. Iijima, M. and Devreotes, P. (2002) Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599-610
71. Innocenti, M., Frittoli, E., Ponzanelli, I., Falck, J.R., Brachmann, S.M., Di Fiore, P.P. and Scita, G. (2003) Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1. J. Cell Biol. 160, 17-23
72. Jaffe, A.B. and Hall, A. (2005) Rho GTPases: biochemistry and biology. Annu. Rev. Cell Dev. Biol. 21, 247-269
73. Janetopoulos, C., Me, L., Devreotes, RN. and Iglesias, P.A. (2004) Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton. Proc. Nati. Aced. Sci. U.S.A. 101, 8951-8956
74. Jones, G.E., Prigmore, E., Calvez, R., Hogan, C., Dunn, G.A., Hirsch, E., Wymann, M.P. and Ridley, A.J. (2003) Requirement for PI 3-kinase γ in macrophage migration to MCP-1 and CSF-1. Exp. Cell Res. 290, 120-131
75. Jones, M.C., Caswell, P.T. and Norman, J.C. (2006) Endocytic recycling pathways: emerging regulators of cell migration. Curr. Opin. Cell Biol. 18, 549-557
76. Jou, S.T., Carpino, N., Takahashi, Y., Piekorz, R., Chao, J.R., Carpino, N., Wang, D. and Ihle, J.N. (2002) Essential, nonredundant role for the phosphoinositide 3-kinase p110δ in signaling by the B-cell receptor complex. Mol. Cell. Biol. 22, 8580-8591
77. Kelley, L.C., Shahab, S. and Weed, S.A. (2008) Actin cytoskeletal mediators of motility and invasion amplified and overexpressed in head and neck cancer. Clin. Exp. Metastasis 25, 289-304
78. Kiosses, W.B., Shattil, S.J., Pampori, N. and Schwartz, M.A. (2001) Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration. Nat. Cell Biol. 3, 316-320
79. Knight, Z.A., Gonzalez, B., Feldman, M.E., Zunder, E.R., Goldenberg, D.D., Williams, O., Loewith, R., Stokoe, D., Balla, A., Toth, B., Balla, T., Weiss, W.A., Williams, R.L. and and Shokat, K.M. (2006) A pharmacological map of the P13-K family defines a role for p110α in insulin signaling. Cell 125, 733-747
80. Kovacs, E.M., Ali, R.G., McCormack, A.J. and Yap, A.S. (2002) E-cadherin homophilic ligation directly signals through Rac and phosphatidylinositol 3-kinase to regulate adhesive contacts. J. Biol. Chem. 277, 6708-6718
81. Kraemer, A., Goodwin, M., Verma, S., Yap, A.S. and Ali, R.G. (2007) Rac is a dominant regulator of cadherin-directed actin assembly that is activated by adhesive ligation independently of Tiam1. Am. J. Physiol. Cell Physiol. 292, C10611-C1069
82. Lammermann, T., Bader, B.L., Monldey, S.J., Worbs, T., Wedlich-Soldner, R., Hirsch, K., Keller, M., Forster, R., Critchley, D.R., Fassler, R. and Sixt, M. (2008) Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453, 51-55
83. Langridge, P.D. and Kay, R.R. (2006) Blabbing of Dictyostelium cells in response to chemoattractant. Exp. Cell Res. 312, 2009-2017
84. Lauffenburger, DA. and Horwitz, A.F. (1996) Cell migration: a physically integrated molecular process. Cell 84, 359-369
85. Lee, J., Ishihara, A., Theriot, J.A. and Jacobson, K. (1993) Principles of locomotion for simple-shaped cells. Nature 362, 167-171
86. Lee, T.H., Avraham, H.K., Jiang, S. and Avraham, S. (2003) Vascular endothelial growth factor modulates the transendothelial migration of MDA-MB-231 breast cancer cells through regulation of brain microvascular endothelial cell permeability. J. Biol. Chem. 278, 5277-5284
87. Lee, J.S., Hmama, Z., Mui, A. and Reiner, N.E. (2004) Stable gene silencing in human monocytic cell lines using lentiviral-delivered small interference RNA. Silencing of the p110α isoform of phosphoinositide 3-kinase reveals differential regulation of adherence induced by 1 α,25-dihydroxycholecalciferol and bacterial lipopolysaccharide. J. Biol. Chem. 279, 9379-9388
88. Li, X., Tupper, J.C., Bannerman, D.D., Winn, R.K., Rhodes, C.J. and Harlan, J.M. (2003) Phospholnositide 3 kinase mediates Toll-like receptor 4-induced activation of NF-κB in endothelial cells. Infect. Immun. 71, 4414-4420
89. Li, Z., Jiang, H., Yie, W., Zhang, Z., Smrcka, A.V. and Wu, D. (2000) Roles of PLC-β2 and -β3 and P13Kγ in chemoattractant-mediated signal transduction. Science 287, 1046-1049
90. Li, Z., Dong, X., Wang, Z., Liu, W., Deng, N., Ding, Y., Tang, L., Hla, T, Zeng, R., Li, L. and Wu, D. (2005) Regulation of PTEN by Rho small GTPases. Nat. Cell Biol. 7, 399-404
91. Lian, L., Wang, Y., Draznin, J., Eslin, D., Bennett, J.S., Poncz, M., Wu, D. and Abrams, C.S. (2005) The relative role of PLCβ and PI3Kγ in platelet activation. Blood 106, 110-117
92. Liu, L., Puri, K.D., Penninger, J.M. and Kubes, P. (2007) Leukocyte PI3Kγ and PI3Kδ have temporally distinct roles for leukocyte recruitment in vivo. Blood 110, 1191-1198
93. Loovers, H.M., Postma, M., Keizer-Gunnink, I., Huang, Y.E., Devreotes, P.N. and van Haastert, P.J. (2006) Distinct roles of PI(3,4,5)P3 during chemoattractant signaling in Dictyostelium: a quantitative in vivo analysis by inhibition of PI3-kinase. Mol. Biol. Cell 17, 1503-1513
94. Maffucci, T., Cooke, F.T., Foster, F.M., Thaer, G.J., Fry, M.J. and Falasca, M. (2005) Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J. Cell Biol. 169, 789-799
95. Martin, A.L., Schwartz, M.D., Jameson, S.C. and Shimizu, Y. (2008) Selective regulation of CD8 effector T cell migration by the p110γ isoform of phosphatidylinositol 3-kinase. J. Immunol. 180, 2081-2088
96. McLachlan, R.W., Kraemer, A., Helwani, F.M., Kovacs, E.M. and Yap, A.S. (2007) E-cadherin adhesion activates c-Src signaling at cell-cell contacts. Mol. Biol. Cell 18, 3214-3223
97. Merlot, S. and Firtel, R.A. (2003) Leading the way: directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J. Cell Sci. 116, 3471-3478
98. Milian, J. and Ridley, A.J. (2005) Rho GTPases and leucocyte-induced endothelial remodelling. Biochem. J. 385, 329-337
99. Milian, J., Hewlett, L., Glyn, M., Toomre, D., Clark, P. and Ridley, A.J. (2006) Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actin-rich domains. Nat. Cell Biol. 8, 113-123
100. Min, J.K., Kim, Y.M., Kim, S.W., Kwon, M.C., Kong, Y.Y., Hwang, I.K., Won, M.H., Rho, J. and Kwon, Y.G. (2005) TNF-related activation-induced cytokine enhances leukocyte adhesiveness: induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-κB activation in endothelial cells. J. Immunol. 175, 531-540
101. Montell, D.J. (2003) Border-cell migration: the race is on. Nat. Rev. Mol. Cell. Biol. 4, 13-24
102. Montell, D.J. (2006) The social lives of migrating cells in Drosophila. Curr. Opin. Genet. Dev. 16, 374-383
103. Murphy, A.M. and Montell, D.J. (1996) Cell type-specific roles for Cdc42, Rac, and RhoL in Drosophila oogenesis. J. Cell Biol. 133, 617-630
104. Naccache, P.H., Levasseur, S., Lachance, G., Chakravarti, S., Bourgoin, S.G. and McColl, S.R. (2000) Stimulation of human neutrophils by chemotactic factors is associated with the activation of phosphatidylinositol 3-kinase γ. J. Biol. Chem. 275, 23636-23641
105. Nakhael-Nejad, M., Hussain, A.M., Zhang, Q.-X. and Murray, A.G. (2007) Endothelial PI 3-kinase activity regulates lymphocyte diapedesis. Am. J. Physiol. Heart Circ. Physiol. 293, H3608-H3616
106. 3 phosphatase SHIP1. Nat. Cell Blol. 9, 36-44
107. 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. (2004) Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing. Immunity 21, 429-441
108. Nombela-Arrieta, C., Mempel, TR., Soriano, S.F., Mazo, I., Wymann, M.P., Hirsch, E., Martínez, A.C., Fukui, Y., von Andrian, U.H. and Stein, J.V. (2007) A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1 -phosphate-mediated egress. J. Exp. Med. 204,497-510
109. Norman, M.U. and Hickey, M.J. (2005) Mechanisms of lymphocyte migration in autoimmune disease. Tissue Antigens 66, 163-172
110. Nourshargh, S. and Marelli-Berg, F.M. (2005) Transmigration through venular walls: a key regulator of leukocyte phenotype a nd function. Trends Immunol. 26, 157-165
111. Oak, J.S., Matheu, M.P., Parker, I., Cahalan, M.D. and Fruman, D.A. (2007) Lymphocyte cell motility: the twisting, turning tale of phosphoinositide 3-kinase. Biochem. Soc. Trans. 35(Pt 5): 1109-1113
112. Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W., Meek, S.E., Salpekar, A., Waterfield, M.D., Smith, A.J. and Vanhaesebroeck, B. (2002) Impaired B and T cell antigen receptor signaling in p1 10δ Pl 3-kinase mutant mice. Science 297, 1031-1034
113. Papakonstanti, E.A., Ridley, A.J. and Vanhaesebroeck, B. (2007) The p1 10δ isoform of Pl 3-kinase negatively controls RhoA and PTEN. EMBO J. 26, 3050-3061
114. Patrucco, E., Notte, A., Barberis, L, Selvetella, G., Maffei, A., Brancaccio, M., Marengo, S., Russo, G., Azzolino, O., Rybalkin, S.D., Silengo, L., Altruda, F., Wetzker, R., Wymann, M.P., Lembo, G. and Hirsch, E. (2004) P13K-γ modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Cell 118, 375-387
115. Pece, S., Chiariello, M., Murga, C. and Gutkind, J.S. (1999) Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell-cell junctions. Evidence for the association of phosphatidylinositol 3-kinase with the E-cadherin adhesion complex. J. Biol. Chem. 274, 19347-19351
116. Pegtel, D.M., Ellenbroek, S.I., Mertens, A.E., van der Kammen, R.A., de Rooij, J. and Collard, J.G. (2007) The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity. Curr. Biol. 17, 1623-1634
117. Pertz, O., Hodgson, L., Klemke, R.L. and Hahn, K.M. (2006) Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 440, 1069-1072
118. Pinho, V., de Castro Russo, R., Amaral, F.A., de Sousa, L.P., Barsante, M.M., de Souza, D.G., Alves-Filho, J.C., Cara, D.C., Hayflick, J.S., Rommel, C., Ruckle, T, Rossi, A.G. and Teixeira, M.M. (2007) Tissue- and stimulus-dependent role of phosphatidylinositol 3-kinase isoforms for neutrophil recruitment induced by chemoattractants in vivo. J. Immunol. 179, 7891-7898
119. Price, J.T., Tiganis, T., Agarwal, A., Djakiew, D. and Thompson, E.W. (1999) Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositoll 3′-kinase and phospholipase C-dependent mechanism. Cancer Res. 59, 5475-5478
120. Puri, K.D., Doggett, TA., Douangpanya, J., Hou, Y., Tino, W.T., Wilson, T., Graf, T., Clayton, E., Turner, M., Hayflick, J.S. and Diacovo, T.G. (2004) Mechanisms and implications of phosphoinositide 3-kinase δ in promoting neutrophil trafficking into inflamed tissue. Blood 103, 3448-3456
121. Puri, K.D., Doggett, T.A., Huang, C.Y., Douangpanya, J., Hayflick, J.S., Turner, M., Penninger, J. and Diacovo, T.G. (2005) The role of endothelial P13Kγ activity in neutrophil trafficking. Blood 106, 150-157
122. Reif, K., Okkenhaug, K., Sasaki, T., Penninger, J.M., Vanhaesebroeck, B. and Cyster, J.G. (2004) Cutting edge: differential roles for phospholnositide 3-kinases, p1 10γ and p1 10γ, in lymphocyte chemotaxis and homing. J. Immunol. 173, 2236-2240
123. Ridley, A.J. (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 16, 522-529
124. Ridley, A.J., Schwartz, M.A., Burridge, K., Firtel, R.A., Ginsberg, M.H., Borisy, G., Parsons, J.T. and Horwitz, A.R. (2003) Cell migration: integrating signals from front to back. Science 302, 1704-1709
125. Roberts, M.S., Woods, A.J., Dale, T.C., Van Der Sluijs, P. and Norman, J.C. (2004) Protein kinase B/Akt acts via glycogen synthase kinase 3 to regulate recycling of αvβ3 and α5β1 integrins. Mol. Cell. Biol. 24, 1505-1515
126. Roymans, D. and Slegers, H. (2001) Phosphatidylinositol 3-kinases in tumor progression. Eur. J. Biochem. 268, 487-498
127. Sadhu, C., Masinovsky, B., Dick, K., Sowell, C.G. and Staunton, D.E. (2003) Essential role of phosphoinositide 3-kinase δ in neutrophil directional movement. J. Immunol. 170, 2647-2654
128. Sahai, E. (2007) Illuminating the metastatic process. Nat Rev Cancer 7, 737-749
129. Sahai, E. and Marshall, C.J. (2003) Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat. Cell Biol. 5, 711-719
130. Sanchez, T., Thangada, S., Wu, M.T., Kontos, C.D., Wu, D., Wu, H. and Hla, T. (2005) PTEN as an effector in the signaling of antimigratory G protein-coupled receptor. Proc. Natl. Acad. Sci. U.S.A. 102, 4312-4317
131. Sasaki, T., Irie-Sasaki, J., Jones, R.G., Oliveira-dos-Santos, A.J., Stanford, W.L., Bolon, B., Wakeham, A., Itie, A., Bouchard, D., Kozieradzkl, I., Joza, N., Mak, T.W., Ohashi, P.S., Suzuki, A. and Penninger, J.M. (2000) Function of PI3Kγ in thymocyte development, T cell activation, and neutrophil migration. Science 287, 1040-1046
132. Sawyer, C., Sturge, J., Bennett, D.C., O'Hare, M.J., Allen, W.E., Bain, J., Jones, G.E. and Vanhaesebroeck, B. (2003) Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110δ. Cancer Res. 63, 1667-1675
133. Schmidt, A. and Hall, A. (2002) Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 16, 1587-1609
134. Schneider, I.C. and Haugh, J.M. (2005) Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts. J. Cell Biol. 171, 883-892
135. Sivamani, K.R., Garcia, M.S. and Isseroff, R.R. (2007) Wound re-epithelialization: modulating keratinocyte migration in wound healing. Front. Biosci. 12, 2849-2868
136. Smit, M.J., Verdijk, P., van der Raaij-Helmer, E.M., Nevis, M., Hensbergen, P.J., Leurs, R. and Tensen, C.P. (2003) CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/ PI-3 kinase. Blood 102, 1959-1965
137. Smith, D.F., Deem, T.L., Bruce, A.C., Reutershan, J., Wu, D. and Ley, K. (2006) Leukocyte phosphoinositide-3 kinase γ is required for chemokine-induced, sustained adhesion under flow in vivo. J. Leukoc. Biol. 80, 1491-1499
138. Smith, L.D., Hickman, E.S., Parry, R.V., Westwick, J. and Ward, S.G. (2007) PI3Kγ is the dominant isoform involved in migratory responses of human T lymphocytes: effects of ex vivo maintenance and limitations of non-viral delivery of siRNA. Cell Signal. 19, 2528-2539
139. Somanath, P.R., Kandel, E.S., Hay, N. and Byzova, T.V. (2007) Akt1 signaling regulates integrin activation, matrix recognition, and fibronectin assembly. J. Biol. Chem. 282, 22964-22976
140. Sossey-Alaoui, K., Li, X., Ranalli, T.A. and Cowell, J.K. (2005) WAVE3-mediated cell migration and lamellipodia formation are regulated downstream of phosphatidylinositol 3-kinase. J. Biol. Chem. 280, 21748-21755
141. Sotsios, Y., Whittaker, G.C., Westwick, J. and Ward, S.G. (1999) The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes. J. Immunol. 163, 5954-5963
142. Stephens, L., Williams, R. and Hawkins, P. (2005) Phosphoinositide 3-kinases as drug targets in cancer. Curr. Opin. Pharmacol. 5, 357-365
143. Suire, S., Coadwell, J., Ferguson, G.J., Davidson, K., Hawkins, P. and Stephens, L. (2005) p84, a new Gβγ-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110γ. Curr. Biol. 15, 566-570
144. Tadokoro, S., Shattil, S.J., Eto, K., Thi, V., Liddington, R.C., de Pereda, J.M., Ginsberg, M.H. and Calderwood, D.A. (2003) Talin binding to integrin β tails: a final common step in integrin activation. Science 302, 103-106
145. Takenawa, T. and Suetsugu, S. (2007) The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol. Cell. Biol. 8, 37-48
146. Tan, M., Grijalva, R. and Yu, D. (1999) Heregulin β1-activated phosphatidylinositol 3-kinase enhances aggregation of MCF-7 breast cancer cells independent of extracellular signal-regulated kinase. Cancer Res. 59, 1620-1625
147. Vanhaesebroeck, B., Jones, G.E., Alen, W.E., Zicha, D., Hooshmand-Rad, R., Sawyer, C., Wells, C., Waterfield, M.D. and Ridley, A.J. (1999) Distinct PI(3)Ks mediate mitogenic signalling and cell migration in macrophages. Nat. Cell Biol. 1, 69-71
148. Vanhaesebroeck, B., Leevers, S.J., Ahmadi, K., Timms, J., Katso, R., Driscoll, P.C., Woscholski, R., Parker, P.J. and Waterfield, M.D. (2001) Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 70, 535-602
149. Vanhaesebroeck, B., Ali, K., Bilancio, A., Gearing, B. and Foukas, L.C. (2005) Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem. Sci. 30, 194-204
150. Veltman, D.M., Keizer-Gunnik, I. and Van Haastert, P.J. (2008) Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum. J. Cell Biol. 180, 747-753
151. Virbasius, J.V., Guilherme, A. and Czech, M.P. (11996) Mouse p170 is a novel phosphaticlyfinositol 3-kinase containing a C2 domain. J. Biol. Chem. 271, 13304-13307
152. Ward, S.G. (2004) Do phosphoinositide 3-kinases direct lymphocyte navigation? Trends Immunol. 25, 67-74
153. Wegener, K.L., Partridge, A.W., Han, J., Pickford, A.R., Liddington, R.C., Ginsberg, M.H. and Campbell, I.D. (2007) Structural basis of integrin activation by talin. Cell 128, 171-182
154. Weiss-Haljiti, C., Pasquali, C., Ji, H., Gillieron, C., Chabert, C., Curchod, M.L., Hirsch, E., Ridley, A.J., van Huijsduijnen, R.H., Camps, M. and Rommel, C. (2004) Involvement of phosphoinositide 3-kinase γ, Rac, and PAK signaling in chemokine-induced macrophage migration. J. Biol. Chem. 279, 43273-43284
155. 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. (2002) P-Rex1, a Ptdins(3,4,5)P3- and Gβγ-regulated guanine-nucleotide exchange factor for Rac. Cell 108, 809-821
156. Welch, H.C., Coadwell, W.J., Stephens, L.R. and Hawkins, P.T. (2003) Phosphoinositide 3-kinase-dependent activation of Rac. FEBS Lett. 546, 93-97
157. Woenckhaus, J., Steger, K., Werner, E., Fenic, I., Gamerdinger, U., Dreyer, T. and Stahl, U. (2002) Genomic gain of PIK3CA and increased expression of p110γ are associated with progression of dysplasia into invasive squamous cell carcinoma. J. Pathol. 198, 335-342
158. Worth, D.C. and Parsons, M. (2008) Adhesion dynamics: Mechanisms and measurements. Int. J. Biochem. Cell Biol. 40, 2397-2409
159. Worthylake, R.A. and Burridge, K. (2001) Leukocyte transendothelial migration: orchestrating the underlying molecular machinery. Curr. Opin.
160. Xi, X., Flevaris, P., Stojanovic, A., Chishti, A., Phillips, D.R., Lam, S.C. and Du, X. (2006) Tyrosine phosphorylation of the integrin β 3 subunit regulates β 3 cleavage by calpain. J. Biol. Chem. 281, 29426-29430
161. Yin, H.L. and Janmey, P.A. (2003) Phosphoinositide regulation of the actin cytoskeleton. Annu. Rev. Physiol. 65, 761-789
162. Yip, S.C., El-Sibai, M., Coniglio, S.J., Mouneimne, G., Eddy, R.J., Drees, B.E., Neilsen, P.O., Goswami, S., Symons, M., Condeelis, J.S. and Backer, J.M. (2007) The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration. J. Cell Sci. 120, 3138-3146
163. Yoshida, K. and Soldati, T. (2006) Dissection of amoeboid movement into two mechanically distinct modes. J. Cell Sci. 119, 3833-3844
164. Zerial, M. and McBride, H. (2001) Rab proteins as membrane organizers. Nat. Rev. Mol. Cell. Biol. 2, 107-117
165. Zinselmeyer, B.H., Lynch, J.N., Zhang, X., Aoshi, T. and Miller, M.J. (2008) Video-rate two-photon imaging of mouse footpad - a promising model for studying leukocyte recruitment dynamics during inflammation. Inflamm. Res. 57, 93-96
166. Zutter, M.M. (2007) Integrin-mediated adhesion: tipping the balance between chemosensitivity and chemoresistance. Adv. Exp. Med. Biol. 608, 87-100