PIP Kinases from the Cell Membrane to the Nucleus

  • Mark Schramp
  • Andrew Hedman
  • Weimin Li
  • Xiaojun Tan
  • Richard AndersonEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 58)


Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane bound lipid molecule with capabilities to affect a wide array of signaling pathways to regulate very different cellular processes. PIP2 is used as a precursor to generate the second messengers PIP3, DAG and IP3, indispensable molecules for signaling events generated by membrane receptors. However, PIP2 can also directly regulate a vast array of proteins and is emerging as a crucial messenger with the potential to distinctly modulate biological processes critical for both normal and pathogenic cell physiology. PIP2 directly associates with effector proteins via unique phosphoinositide binding domains, altering their localization and/or enzymatic activity. The spatial and temporal generation of PIP2 synthesized by the phosphatidylinositol phosphate kinases (PIPKs) tightly regulates the activation of receptor signaling pathways, endocytosis and vesicle trafficking, cell polarity, focal adhesion dynamics, actin assembly and 3’ mRNA processing. Here we discuss our current understanding of PIPKs in the regulation of cellular processes from the plasma membrane to the nucleus.


Cell Migration mRNA processing Phosphatidylinositol phosphate kinase (PIPK) Phosphatidylinositol 4,5-bisphosphate (PIP2Vesicle trafficking 



We apologize to those whose work could not be cited due to space limitations. We thank Suyong Choi, Yue Sun and Rakesh Singh for their scientific discussions and comments on the manuscript prior to submission. Structures rendered in The PyMOL Molecular Graphics System, Version 1.3, Schrödinger, LLC. Research in the authors’ lab is supported by NIH grants GM057549, GM051968 and CA104708.


  1. Akiyama C, Shinozaki-Narikawa N, Kitazawa T, Hamakubo T, Kodama T, Shibasaki Y (2005) Phosphatidylinositol-4-phosphate 5-kinase gamma is associated with cell-cell junction in A431 epithelial cells. Cell Biol Int 29:514–520CrossRefPubMedGoogle Scholar
  2. Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC (1999) Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes. J Biol Chem 274:9907–9910CrossRefPubMedGoogle Scholar
  3. Audhya A, Emr SD (2003) Regulation of PI4,5P2 synthesis by nuclear-cytoplasmic shuttling of the Mss4 lipid kinase. EMBO J 22:4223–4236CrossRefPubMedGoogle Scholar
  4. Bading H, Hardingham GE, Johnson CM, Chawla S (1997) Gene regulation by nuclear and cytoplasmic calcium signals. Biochem Biophys Res Commun 236:541–543CrossRefPubMedGoogle Scholar
  5. Bai J, Tucker WC, Chapman ER (2004) PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane. Nat Struct Mol Biol 11:36–44CrossRefPubMedGoogle Scholar
  6. Bairstow SF, Ling K, Su X, Firestone AJ, Carbonara C, Anderson RA (2006) Type Igamma661 phosphatidylinositol phosphate kinase directly interacts with AP2 and regulates endocytosis. J Biol Chem 281:20632–20642CrossRefPubMedGoogle Scholar
  7. Bakolitsa C, Cohen DM, Bankston LA, Bobkov AA, Cadwell GW, Jennings L, Critchley DR, Craig SW, Liddington RC (2004) Structural basis for vinculin activation at sites of cell adhesion. Nature 430:583–586CrossRefPubMedGoogle Scholar
  8. Barlow CA, Laishram RS, Anderson RA (2010) Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum. Trends Cell Biol 20:25–35CrossRefPubMedGoogle Scholar
  9. Bazenet CE, Ruano AR, Brockman JL, Anderson RA (1990) The human erythrocyte contains two forms of phosphatidylinositol-4-phosphate 5-kinase which are differentially active toward membranes. J Biol Chem 265:18012–18022PubMedGoogle Scholar
  10. Bonifacino J, Traub L (2003) Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 72:395–447CrossRefPubMedGoogle Scholar
  11. Boronenkov IV, Anderson RA (1995) The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases. J Biol Chem 270:2881–2884CrossRefPubMedGoogle Scholar
  12. Boronenkov IV, Loijens JC, Umeda M, Anderson RA (1998) Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol Biol Cell 9:3547–3560PubMedGoogle Scholar
  13. Broussard JA, Webb DJ, Kaverina I (2008) Asymmetric focal adhesion disassembly in motile cells. Curr Opin Cell Biol 20:85–90CrossRefPubMedGoogle Scholar
  14. Bultsma Y, Keune WJ, Divecha N (2010) PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. Biochem J 430:223–235CrossRefPubMedGoogle Scholar
  15. Bunce MW, Bergendahl K, Anderson RA (2006a) Nuclear PI(4,5)P(2): a new place for an old signal. Biochim Biophys Acta 1761:560–569CrossRefGoogle Scholar
  16. Bunce MW, Gonzales ML, Anderson RA (2006b) Stress-ING out: phosphoinositides mediate the cellular stress response. Sci STKE 2006:pe46Google Scholar
  17. Bunce MW, Boronenkov IV, Anderson RA (2008) Coordinated activation of the nuclear ubiquitin ligase Cul3-SPOP by the generation of phosphatidylinositol 5-phosphate. J Biol Chem 283:8678–8686CrossRefPubMedGoogle Scholar
  18. Burden LM, Rao VD, Murray D, Ghirlando R, Doughman SD, Anderson RA, Hurley JH (1999) The flattened face of type II beta phosphatidylinositol phosphate kinase binds acidic phospholipid membranes. Biochemistry 38:15141–15149CrossRefPubMedGoogle Scholar
  19. Burridge K, Sastry SK, Sallee JL (2006) Regulation of cell adhesion by protein-tyrosine phosphatases. I. Cell-matrix adhesion. J Biol Chem 281:15593–15596CrossRefPubMedGoogle Scholar
  20. Cabezas A, Pattni K, Stenmark H (2006) Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1. Gene 371:34–41CrossRefPubMedGoogle Scholar
  21. Caswell PT, Norman JC (2006) Integrin trafficking and the control of cell migration. Traffic 7:14–21CrossRefPubMedGoogle Scholar
  22. Chandrasekar I, Stradal TE, Holt MR, Entschladen F, Jockusch BM, Ziegler WH (2005) Vinculin acts as a sensor in lipid regulation of adhesion-site turnover. J Cell Sci 118:1461–1472CrossRefPubMedGoogle Scholar
  23. Chao WT, Kunz J (2009) Focal adhesion disassembly requires clathrin-dependent endocytosis of integrins. FEBS Lett 583:1337–1343CrossRefPubMedGoogle Scholar
  24. Chao WT, Ashcroft F, Daquinag AC, Vadakkan T, Wei Z, Zhang P, Dickinson ME, Kunz, J (2010) Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting beta1 integrin endocytosis. Mol Cell Biol 30:4463–4479Google Scholar
  25. Chao WT, Daquinag AC, Ashcroft F, Kunz, J (2010) Type I PIPK-alpha regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation. J Cell Biol 190:247–262Google Scholar
  26. Chatah NE, Abrams CS (2001) G-protein-coupled receptor activation induces the membrane translocation and activation of phosphatidylinositol-4-phosphate 5-kinase I alpha by a Rac- and Rho-dependent pathway. J Biol Chem 276:34059–34065CrossRefPubMedGoogle Scholar
  27. Ciruela A, Hinchliffe KA, Divecha N, Irvine RF (2000) Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7. Biochem J 346(Pt 3):587–591CrossRefPubMedGoogle Scholar
  28. Clarke JH, Letcher AJ, D’Santos C S, Halstead JR, Irvine RF, Divecha N (2001) Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells. Biochem J 357:905–910CrossRefPubMedGoogle Scholar
  29. Cocco L, Gilmour RS, Ognibene A, Letcher AJ, Manzoli FA, Irvine RF (1987) Synthesis of polyphosphoinositides in nuclei of Friend cells. Evidence for polyphosphoinositide metabolism inside the nucleus which changes with cell differentiation. Biochem J 248:765–770PubMedGoogle Scholar
  30. Cocco L, Martelli AM, Gilmour RS, Ognibene A, Manzoli FA, Irvine RF (1988) Rapid changes in phospholipid metabolism in the nuclei of Swiss 3T3 cells induced by treatment of the cells with insulin-like growth factor I. Biochem Biophys Res Commun 154:1266–1272CrossRefPubMedGoogle Scholar
  31. Cooke FT, Dove SK, McEwen RK, Painter G, Holmes AB, Hall MN, Michell RH, Parker PJ (1998) The stress-activated phosphatidylinositol 3-phosphate 5-kinase Fab1p is essential for vacuole function in S. cerevisiae. Curr Biol 8:1219–1222CrossRefPubMedGoogle Scholar
  32. Cox S, Taylor SS (1994) Holoenzyme interaction sites in the cAMP-dependent protein kinase. Histidine 87 in the catalytic subunit complements serine 99 in the type I regulatory subunit. J Biol Chem 269:22614–22622PubMedGoogle Scholar
  33. D’Santos CS, Clarke JH, Divecha N (1998) Phospholipid signalling in the nucleus. Een DAG uit het leven van de inositide signalering in de nucleus. Biochim Biophys Acta 1436:201–232CrossRefPubMedGoogle Scholar
  34. Del Pozo MA, Kiosses WB, Alderson NB, Meller N, Hahn KM, Schwartz MA (2002) Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Nat Cell Biol 4:232–239CrossRefPubMedGoogle Scholar
  35. Dell’Angelica E, Mullins C, Bonifacino J (1999) AP-4, a novel protein complex related to clathrin adaptors. J Biol Chem 274:7278–7285CrossRefPubMedGoogle Scholar
  36. DeMali KA, Barlow CA, Burridge K (2002) Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J Cell Biol 159:881–891CrossRefPubMedGoogle Scholar
  37. Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–657CrossRefPubMedGoogle Scholar
  38. Di Paolo G, Pellegrini L, Letinic K, Cestra G, Zoncu R, Voronov S, Chang S, Guo J, Wenk MR, De Camilli P (2002) Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin. Nature 420:85–89CrossRefPubMedGoogle Scholar
  39. Di Paolo G, Moskowitz HS, Gipson K, Wenk MR, Voronov S, Obayashi M, Flavell R, Fitzsimonds RM, Ryan TA, De Camilli P (2004) Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking. Nature 431:415–422CrossRefPubMedGoogle Scholar
  40. Didichenko SA, Thelen M (2001) Phosphatidylinositol 3-kinase c2alpha contains a nuclear localization sequence and associates with nuclear speckles. J Biol Chem 276:48135–48142PubMedGoogle Scholar
  41. Divecha N, Roefs M, Los A, Halstead J, Bannister A, D’Santos C (2002) Type I PIPkinases interact with and are regulated by the retinoblastoma susceptibility gene product-pRB. Curr Biol 12:582–587CrossRefPubMedGoogle Scholar
  42. Doughman RL, Firestone AJ, Anderson RA (2003a) Phosphatidylinositol phosphate kinases put PI4,5P(2) in its place. J Membr Biol 194:77–89CrossRefGoogle Scholar
  43. Doughman RL, Firestone AJ, Wojtasiak ML, Bunce MW, Anderson RA (2003b) Membrane ruffling requires coordination between type Ialpha phosphatidylinositol phosphate kinase and Rac signaling. J Biol Chem 278:23036–23045CrossRefGoogle Scholar
  44. Dumas F, Byrne RD, Vincent B, Hobday TM, Poccia DL, Larijani B (2010) Spatial regulation of membrane fusion controlled by modification of phosphoinositides. PLoS One 5:e12208Google Scholar
  45. Ezratty EJ, Partridge MA, Gundersen GG (2005) Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7:581–590CrossRefPubMedGoogle Scholar
  46. Fölsch H, Ohno H, Bonifacino J, Mellman I (1999) A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells. Cell 99:189–198CrossRefPubMedGoogle Scholar
  47. Franco SJ, Huttenlocher A (2005) Regulating cell migration: calpains make the cut. J Cell Sci 118:3829–3838CrossRefPubMedGoogle Scholar
  48. Franco SJ, Rodgers MA, Perrin BJ, Han J, Bennin DA, Critchley DR, Huttenlocher A (2004) Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol 6:977–983CrossRefPubMedGoogle Scholar
  49. Gaidarov I, Krupnick JG, Falck JR, Benovic JL, Keen JH (1999) Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding. Embo J 18:871–881CrossRefPubMedGoogle Scholar
  50. Garnier-Lhomme M, Byrne RD, Hobday TM, Gschmeissner S, Woscholski R, Poccia DL, Dufourc EJ, Larijani B (2009) Nuclear envelope remnants: fluid membranes enriched in sterols and polyphosphoinositides. PLoS One 4:e4255Google Scholar
  51. Gary JD, Wurmser AE, Bonangelino CJ, Weisman LS, Emr SD (1998) Fab1p is essential for PtdIns(3)P 5-kinase activity and the maintenance of vacuolar size and membrane homeostasis. J Cell Biol 143:65–79CrossRefPubMedGoogle Scholar
  52. Gong LW, Di Paolo G, Diaz E, Cestra G, Diaz ME, Lindau M, De Camilli P, Toomre D (2005) Phosphatidylinositol phosphate kinase type I gamma regulates dynamics of large dense-core vesicle fusion. Proc Natl Acad Sci U S A 102:5204–5209CrossRefPubMedGoogle Scholar
  53. Gonzales ML, Anderson RA (2006) Nuclear phosphoinositide kinases and inositol phospholipids. J Cell Biochem 97:252–260CrossRefPubMedGoogle Scholar
  54. Gonzales ML, Mellman DL, Anderson RA (2008) CKIalpha is associated with and phosphorylates star-PAP and is also required for expression of select star-PAP target messenger RNAs. J Biol Chem 283:12665–12673CrossRefPubMedGoogle Scholar
  55. Gorbatyuk VY, Nosworthy NJ, Robson SA, Bains NP, Maciejewski MW, Dos Remedios CG, King GF (2006) Mapping the phosphoinositide-binding site on chick cofilin explains how PIP2 regulates the cofilin-actin interaction. Mol Cell 24:511–522CrossRefPubMedGoogle Scholar
  56. Goss VL, Hocevar BA, Thompson LJ, Stratton CA, Burns DJ, Fields AP (1994) Identification of nuclear beta II protein kinase C as a mitotic lamin kinase. J Biol Chem 269:19074–19080PubMedGoogle Scholar
  57. Gurr MI, Finean JB, Hawthorne JN (1963) The phospholipids of liver-cell fractions. I. The phospholipid composition of the liver-cell nucleus. Biochim Biophys Acta 70:406–416CrossRefPubMedGoogle Scholar
  58. Hall A, Nobes CD (2000) Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Philos Trans R Soc Lond B Biol Sci 355:965–970CrossRefPubMedGoogle Scholar
  59. Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9:576–596PubMedGoogle Scholar
  60. Hanks SK, Quinn AM, Hunter T (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241:42–52CrossRefPubMedGoogle Scholar
  61. Hardingham GE, Chawla S, Johnson CM, Bading H (1997) Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression. Nature 385:260–265CrossRefPubMedGoogle Scholar
  62. Hay JC, Fisette PL, Jenkins GH, Fukami K, Takenawa T, Anderson RA, Martin TF (1995) ATP-dependent inositide phosphorylation required for Ca(2+)-activated secretion. Nature 374:173–177CrossRefPubMedGoogle Scholar
  63. He B, Xi F, Zhang X, Zhang J, Guo W (2007) Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane. EMBO J 26:4053–4065CrossRefPubMedGoogle Scholar
  64. Heck JN, Mellman DL, Ling K, Sun Y, Wagoner MP, Schill NJ, Anderson RA (2007) A conspicuous connection: structure defines function for the phosphatidylinositol-phosphate kinase family. Crit Rev Biochem Mol Biol 42:15–39CrossRefPubMedGoogle Scholar
  65. Hinchliffe KA, Irvine RF (2006) Regulation of type II PIP kinase by PKD phosphorylation. Cell Signal 18:1906–1913CrossRefPubMedGoogle Scholar
  66. Hinchliffe KA, Ciruela A, Letcher AJ, Divecha N, Irvine RF (1999a) Regulation of type IIalpha phosphatidylinositol phosphate kinase localisation by the protein kinase CK2. Curr Biol 9:983–986CrossRefGoogle Scholar
  67. Hinchliffe KA, Ciruela A, Morris JA, Divecha N, Irvine RF (1999b) The type II PIPkins (PtdIns5P 4-kinases): enzymes in search of a function? Biochem Soc Trans 27:657–661Google Scholar
  68. Hokin MR, Hokin LE (1953) Enzyme secretion and the incorporation of P32 into phospholipides of pancreas slices. J Biol Chem 203:967–977PubMedGoogle Scholar
  69. Homma K, Terui S, Minemura M, Qadota H, Anraku Y, Kanaho Y, Ohya Y (1998) Phosphatidylinositol-4-phosphate 5-kinase localized on the plasma membrane is essential for yeast cell morphogenesis. J Biol Chem 273:15779–15786CrossRefPubMedGoogle Scholar
  70. Honda A, Nogami M, Yokozeki T, Yamazaki M, Nakamura H, Watanabe H, Kawamoto K, Nakayama K, Morris AJ, Frohman MA, Kanaho Y (1999) Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell 99:521–532CrossRefPubMedGoogle Scholar
  71. Höning S, Ricotta D, Krauss M, Späte K, Spolaore B, Motley A, Robinson M, Robinson C, Haucke V, Owen D (2005) Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2. Mol Cell 18:519–531CrossRefPubMedGoogle Scholar
  72. Humbert JP, Matter N, Artault JC, Koppler P, Malviya AN (1996) Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane vindicating regulation of nuclear calcium signaling by inositol 1,4,5-trisphosphate. Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes. J Biol Chem 271:478–485CrossRefPubMedGoogle Scholar
  73. Irvine RF (2003) Nuclear lipid signalling. Nat Rev Mol Cell Biol 4:349–360CrossRefPubMedGoogle Scholar
  74. Ishihara H, Shibasaki Y, Kizuki N, Katagiri H, Yazaki Y, Asano T, Oka Y (1996) Cloning of cDNAs encoding two isoforms of 68-kDa type I phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem 271:23611–23614CrossRefPubMedGoogle Scholar
  75. Ishihara H, Shibasaki Y, Kizuki N, Wada T, Yazaki Y, Asano T, 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 273:8741–8748CrossRefPubMedGoogle Scholar
  76. Itoh T, Ishihara H, Shibasaki Y, Oka Y, Takenawa T (2000) Autophosphorylation of type I phosphatidylinositol phosphate kinase regulates its lipid kinase activity. J Biol Chem 275:19389–19394CrossRefPubMedGoogle Scholar
  77. Iyer GH, Moore MJ, Taylor SS (2005) Consequences of lysine 72 mutation on the phosphorylation and activation state of cAMP-dependent kinase. J Biol Chem 280:8800–8807CrossRefPubMedGoogle Scholar
  78. Jackson T (1998) Transport vesicles: coats of many colours. Curr Biol 8:R609–R612CrossRefPubMedGoogle Scholar
  79. Janmey PA, Lindberg U (2004) Cytoskeletal regulation: rich in lipids. Nat Rev Mol Cell Biol 5:658–666CrossRefPubMedGoogle Scholar
  80. Jenkins GH, Subrahmanyam G, Anderson RA (1991) Purification and reconstitution of phosphatidylinositol 4-kinase from human erythrocytes. Biochim Biophys Acta 1080:11–18CrossRefPubMedGoogle Scholar
  81. Jenkins GH, Fisette PL, Anderson RA (1994) Type I phosphatidylinositol 4-phosphate 5-kinase isoforms are specifically stimulated by phosphatidic acid. J Biol Chem 269:11547–11554PubMedGoogle Scholar
  82. Johnson LN, Noble ME, Owen DJ (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85:149–158CrossRefPubMedGoogle Scholar
  83. Jones DR, Bultsma Y, Keune WJ, Halstead JR, Elouarrat D, Mohammed S, Heck AJ, D’Santos CS, Divecha N (2006) Nuclear PtdIns5P as a transducer of stress signaling: an in vivo role for PIP4Kbeta. Mol Cell 23:685–695CrossRefPubMedGoogle Scholar
  84. Kahlfeldt N, Vahedi-Faridi A, Koo S, Schäfer J, Krainer G, Keller S, Saenger W, Krauss M, Haucke V (2010) Molecular basis for association of PIPKI gamma-p90 with clathrin adaptor AP-2. J Biol Chem 285:2734–2749CrossRefPubMedGoogle Scholar
  85. Keune W, Bultsma Y, Sommer L, Jones D, Divecha N (2010) Phosphoinositide signalling in the nucleus. Adv Enzyme Regul 51(1):91–99Google Scholar
  86. Kisseleva M, Feng Y, Ward M, Song C, Anderson RA, Longmore GD (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 25:3956–3966CrossRefPubMedGoogle Scholar
  87. Kleinig H (1970) Nuclear membranes from mammalian liver. II. Lipid composition. J Cell Biol 46:396–402CrossRefPubMedGoogle Scholar
  88. Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM (1991a) Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science 253:407–414CrossRefGoogle Scholar
  89. Knighton DR, Zheng JH, Ten Eyck LF, Xuong NH, Taylor SS, Sowadski JM (1991b) Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science 253:414–420CrossRefGoogle Scholar
  90. Krauss M, Kinuta M, Wenk MR, De Camilli P, Takei K, Haucke V (2003) ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma. J Cell Biol 162:113–124CrossRefPubMedGoogle Scholar
  91. Krauss M, Kukhtina V, Pechstein A, Haucke V (2006) Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes. Proc Natl Acad Sci U S A 103:11934–11939CrossRefPubMedGoogle Scholar
  92. Krupa A, Preethi G, Srinivasan N (2004) Structural modes of stabilization of permissive phosphorylation sites in protein kinases: distinct strategies in Ser/Thr and Tyr kinases. J Mol Biol 339:1025–1039CrossRefPubMedGoogle Scholar
  93. Kumar N, Khurana S (2004) Identification of a functional switch for actin severing by cytoskeletal proteins. J Biol Chem 279:24915–24918CrossRefPubMedGoogle Scholar
  94. Kumar N, Zhao P, Tomar A, Galea CA, Khurana S (2004) Association of villin with phosphatidylinositol 4,5-bisphosphate regulates the actin cytoskeleton. J Biol Chem 279:3096–3110CrossRefPubMedGoogle Scholar
  95. Kunz J, Wilson MP, Kisseleva M, Hurley JH, Majerus PW, Anderson RA (2000) The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Mol Cell 5:1–11CrossRefPubMedGoogle Scholar
  96. Kunz J, Fuelling A, Kolbe L, Anderson RA (2002) Stereo-specific substrate recognition by phosphatidylinositol phosphate kinases is swapped by changing a single amino acid residue. J Biol Chem 277:5611–5619CrossRefPubMedGoogle Scholar
  97. Kwiatkowska K (2010) One lipid, multiple functions: how various pools of PI(4,5)P(2) are created in the plasma membrane. Cell Mol Life Sci 67:3927–3946CrossRefPubMedGoogle Scholar
  98. Lambrechts A, Jonckheere V, Dewitte D, Vandekerckhove J, Ampe C (2002) Mutational analysis of human profilin I reveals a second PI(4,5)-P2 binding site neighbouring the poly(L-proline) binding site. BMC Biochem 3:12CrossRefPubMedGoogle Scholar
  99. Lamond AI, Spector DL (2003) Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol 4:605–612CrossRefPubMedGoogle Scholar
  100. Lassing I, Lindberg U (1985) Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Nature 314:472–474CrossRefPubMedGoogle Scholar
  101. Lee S, Voronov S, Letinic K, Nairn A, Di Paolo G, De Camilli P (2005) Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases. J Cell Biol 168:789–799CrossRefPubMedGoogle Scholar
  102. Letinic K, Sebastian R, Toomre D, Rakic P (2009) Exocyst is involved in polarized cell migration and cerebral cortical development. Proc Natl Acad Sci U S A 106:11342–11347CrossRefPubMedGoogle Scholar
  103. Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA (2002) Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature 420:89–93CrossRefPubMedGoogle Scholar
  104. Ling K, Doughman RL, Iyer VV, Firestone AJ, Bairstow SF, Mosher DF, Schaller MD, Anderson RA (2003) Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate kinase by Src regulates an integrin-talin switch. J Cell Biol 163:1339–1349CrossRefPubMedGoogle Scholar
  105. Ling K, Schill NJ, Wagoner MP, Sun Y, Anderson RA (2006) Movin’ on up: the role of PtdIns(4,5)P(2) in cell migration. Trends Cell Biol 16:276–284CrossRefPubMedGoogle Scholar
  106. Ling K, Bairstow S, Carbonara C, Turbin D, Huntsman D, Anderson R (2007) Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin. J Cell Biol 176:343–353CrossRefPubMedGoogle Scholar
  107. Liu J, Zuo X, Yue P, Guo W (2007) Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells. Mol Biol Cell 18:4483–4492CrossRefPubMedGoogle Scholar
  108. Loijens JC, Boronenkov IV, Parker GJ, Anderson RA (1996) The phosphatidylinositol 4-phosphate 5-kinase family. Adv Enzyme Regul 36:115–140CrossRefPubMedGoogle Scholar
  109. Lokuta MA, Senetar MA, Bennin DA, Nuzzi PA, Chan KT, Ott VL, Huttenlocher A (2007) Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis. Mol Biol Cell 18:5069–5080CrossRefPubMedGoogle Scholar
  110. Malviya AN, Rogue PJ (1998) “Tell me where is calcium bred”: clarifying the roles of nuclear calcium. Cell 92:17–23CrossRefPubMedGoogle Scholar
  111. Martel V, Racaud-Sultan C, Dupe S, Marie C, Paulhe F, Galmiche A, Block MR, Albiges-Rizo C (2001) Conformation, localization, and integrin binding of talin depend on its interaction with phosphoinositides. J Biol Chem 276:21217–21227CrossRefPubMedGoogle Scholar
  112. Matsui T, Yonemura S, Tsukita S, Tsukita S (1999) Activation of ERM proteins in vivo by Rho involves phosphatidyl-inositol 4-phosphate 5-kinase and not ROCK kinases. Curr Biol 9:1259–1262CrossRefPubMedGoogle Scholar
  113. McEwen RK, Dove SK, Cooke FT, Painter GF, Holmes AB, Shisheva A, Ohya Y, Parker PJ, Michell RH (1999) Complementation analysis in PtdInsP kinase-deficient yeast mutants demonstrates that Schizosaccharomyces pombe and murine Fab1p homologues are phosphatidylinositol 3-phosphate 5-kinases. J Biol Chem 274:33905–33912CrossRefPubMedGoogle Scholar
  114. Mellman DL, Gonzales ML, Song C, Barlow CA, Wang P, Kendziorski C, Anderson RA (2008) A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs. Nature 451:1013–1017CrossRefPubMedGoogle Scholar
  115. Millard TH, Sharp SJ, Machesky LM (2004) Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex. Biochem J 380:1–17CrossRefPubMedGoogle Scholar
  116. Moritz A, De Graan PN, Gispen WH, Wirtz KW (1992a) Phosphatidic acid is a specific activator of phosphatidylinositol-4-phosphate kinase. J Biol Chem 267:7207–7210Google Scholar
  117. Moritz A, Westerman J, De Graan PN, Wirtz KW (1992b) Phosphatidylinositol 4-kinase and phosphatidylinositol-4-phosphate 5-kinase from bovine brain membranes. Methods Enzymol 209:202–211CrossRefGoogle Scholar
  118. Nakano-Kobayashi A, Yamazaki M, Unoki T, Hongu T, Murata C, Taguchi R, Katada T, Frohman M, Yokozeki T, Kanaho Y (2007) Role of activation of PIP5Kgamma661 by AP-2 complex in synaptic vesicle endocytosis. EMBO J 26:1105–1116CrossRefPubMedGoogle Scholar
  119. Nakatsu F, Ohno H (2003) Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct 28:419–429CrossRefPubMedGoogle Scholar
  120. Narkis G, Ofir R, Manor E, Landau D, Elbedour K, Birk OS (2007) Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway. Am J Hum Genet 81:589–595CrossRefPubMedGoogle Scholar
  121. Nayal A, Webb DJ, Horwitz AF (2004) Talin: an emerging focal point of adhesion dynamics. Curr Opin Cell Biol 16:94–98CrossRefPubMedGoogle Scholar
  122. Nicholson-Dykstra S, Higgs HN, Harris ES (2005) Actin dynamics: growth from dendritic branches. Curr Biol 15:R346–R357CrossRefPubMedGoogle Scholar
  123. Niggli V (2005) Regulation of protein activities by phosphoinositide phosphates. Annu Rev Cell Dev Biol 21:57–79CrossRefPubMedGoogle Scholar
  124. Odorizzi G, Babst M, Emr SD (1998) Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 95:847–858CrossRefPubMedGoogle Scholar
  125. Ohno H (2006) Physiological roles of clathrin adaptor AP complexes: lessons from mutant animals. J Biochem 139:943–948CrossRefPubMedGoogle Scholar
  126. Olusanya O, Andrews P, Swedlow J, Smythe E (2001) Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is essential for endocytosis in vitro and in vivo. Curr Biol 11:896–900CrossRefPubMedGoogle Scholar
  127. Osborne SL, Thomas CL, Gschmeissner S, Schiavo G (2001) Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing. J Cell Sci 114:2501–2511PubMedGoogle Scholar
  128. Oztan A, Silvis M, Weisz OA, Bradbury NA, Hsu SC, Goldenring JR, Yeaman C, Apodaca G (2007) Exocyst requirement for endocytic traffic directed toward the apical and basolateral poles of polarized MDCK cells. Mol Biol Cell 18:3978–3992CrossRefPubMedGoogle Scholar
  129. Park SJ, Itoh T, Takenawa T (2001) Phosphatidylinositol 4-phosphate 5-kinase type I is regulated through phosphorylation response by extracellular stimuli. J Biol Chem 276:4781–4787CrossRefPubMedGoogle Scholar
  130. Payrastre B, Nievers M, Boonstra J, Breton M, Verkleij AJ, Van Bergen en Henegouwen PM (1992) A differential location of phosphoinositide kinases, diacylglycerol kinase, and phospholipase C in the nuclear matrix. J Biol Chem 267:5078–5084PubMedGoogle Scholar
  131. Pierini LM, Lawson MA, Eddy RJ, Hendey B, Maxfield FR (2000) Oriented endocytic recycling of alpha5beta1 in motile neutrophils. Blood 95:2471–2480PubMedGoogle Scholar
  132. Prehoda KE, Scott JA, Mullins RD, Lim WA (2000) Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex. Science 290:801–806CrossRefPubMedGoogle Scholar
  133. Prigozhina NL, Waterman-Storer CM (2004) Protein kinase D-mediated anterograde membrane trafficking is required for fibroblast motility. Curr Biol 14:88–98CrossRefPubMedGoogle Scholar
  134. Qualmann B, Kessels MM, Kelly RB (2000) Molecular links between endocytosis and the actin cytoskeleton. J Cell Biol 150:F111–F116CrossRefPubMedGoogle Scholar
  135. Rameh LE, Tolias KF, Duckworth BC, Cantley LC (1997) A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature 390:192–196CrossRefPubMedGoogle Scholar
  136. Rando OJ, Zhao K, Janmey P, Crabtree GR (2002) Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex. Proc Natl Acad Sci U S A 99:2824–2829CrossRefPubMedGoogle Scholar
  137. Rao VD, Misra S, Boronenkov IV, Anderson RA, Hurley JH (1998) Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation. Cell 94:829–839CrossRefPubMedGoogle Scholar
  138. Rohde G, Wenzel D, Haucke V (2002) A phosphatidylinositol (4,5)-bisphosphate binding site within mu2-adaptin regulates clathrin-mediated endocytosis. J Cell Biol 158:209–214CrossRefPubMedGoogle Scholar
  139. Rosse C, Hatzoglou A, Parrini MC, White MA, Chavrier P, Camonis J (2006) RalB mobilizes the exocyst to drive cell migration. Mol Cell Biol 26:727–734CrossRefPubMedGoogle Scholar
  140. Rozelle AL, Machesky LM, Yamamoto M, Driessens MH, Insall RH, Roth MG, Luby-Phelps K, Marriott G, Hall A, Yin HL (2000) Phosphatidylinositol 4,5-bisphosphate induces actin-based movement of raft-enriched vesicles through WASP-Arp2/3. Curr Biol 10:311–320CrossRefPubMedGoogle Scholar
  141. Saraste M, Sibbald PR, Wittinghofer A (1990) The P-loop—a common motif in ATP- and GTP-binding proteins. Trends Biochem Sci 15:430–434CrossRefPubMedGoogle Scholar
  142. Sasaki J, Sasaki T, Yamazaki M, Matsuoka K, Taya C, Shitara H, Takasuga S, Nishio M, Mizuno K, Wada T et al (2005) Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I {alpha}. J Exp Med 201:859–870CrossRefPubMedGoogle Scholar
  143. Sbrissa D, Ikonomov OC, Shisheva A (1999) PIKfyve, a mammalian ortholog of yeast Fab1p lipid kinase, synthesizes 5-phosphoinositides. Effect of insulin. J Biol Chem 274:21589–21597CrossRefPubMedGoogle Scholar
  144. Sbrissa D, Ikonomov OC, Shisheva A (2000) PIKfyve lipid kinase is a protein kinase: downregulation of 5’-phosphoinositide product formation by autophosphorylation. Biochemistry 39:15980–15989CrossRefPubMedGoogle Scholar
  145. Schill N, Anderson R (2009a) Out, in and back again: PtdIns(4,5)P(2) regulates cadherin trafficking in epithelial morphogenesis. Biochem J 418:247–260CrossRefGoogle Scholar
  146. Schill NJ, Anderson RA (2009) Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. Biochem J 422(3):473–482CrossRefPubMedGoogle Scholar
  147. Schmoranzer J, Kreitzer G, Simon SM (2003) Migrating fibroblasts perform polarized, microtubule-dependent exocytosis towards the leading edge. J Cell Sci 116:4513–4519CrossRefPubMedGoogle Scholar
  148. Schramp M, Ying O, Kim TY, Martin GS (2008) ERK5 promotes Src-induced podosome formation by limiting Rho activation. J Cell Biol 181:1195–1210CrossRefPubMedGoogle Scholar
  149. Sechi AS, Wehland J (2000) The actin cytoskeleton and plasma membrane connection: PtdIns(4,5)P(2) influences cytoskeletal protein activity at the plasma membrane. J Cell Sci 113(Pt 21):3685–3695PubMedGoogle Scholar
  150. Shibasaki Y, Ishihara H, Kizuki N, Asano T, Oka Y, Yazaki Y (1997) Massive actin polymerization induced by phosphatidylinositol-4-phosphate 5-kinase in vivo. J Biol Chem 272:7578–7581CrossRefPubMedGoogle Scholar
  151. Shisheva A, Sbrissa D, Ikonomov O (1999) Cloning, characterization, and expression of a novel Zn2+ -binding FYVE finger-containing phosphoinositide kinase in insulin-sensitive cells. Mol Cell Biol 19:623–634PubMedGoogle Scholar
  152. Sidani M, Wessels D, Mouneimne G, Ghosh M, Goswami S, Sarmiento C, Wang W, Kuhl S, El-Sibai M, Backer JM et al (2007) Cofilin determines the migration behavior and turning frequency of metastatic cancer cells. J Cell Biol 179:777–791CrossRefPubMedGoogle Scholar
  153. Skare P, Karlsson R (2002) Evidence for two interaction regions for phosphatidylinositol(4,5)-bisphosphate on mammalian profilin I. FEBS Lett 522:119–124CrossRefPubMedGoogle Scholar
  154. Smith CD, Wells WW (1983a) Phosphorylation of rat liver nuclear envelopes. I. Characterization of in vitro protein phosphorylation. J Biol Chem 258:9360–9367Google Scholar
  155. Smith CD, Wells WW (1983b) Phosphorylation of rat liver nuclear envelopes. II. Characterization of in vitro lipid phosphorylation. J Biol Chem 258:9368–9373Google Scholar
  156. Smith CD, Wells WW (1984a) Characterization of a phosphatidylinositol 4-phosphate-specific phosphomonoesterase in rat liver nuclear envelopes. Arch Biochem Biophys 235:529–537CrossRefGoogle Scholar
  157. Smith CD, Wells WW (1984b) Solubilization and reconstitution of a nuclear envelope-associated ATPase. Synergistic activation by RNA and polyphosphoinositides. J Biol Chem 259:11890–11894Google Scholar
  158. Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature 306:67–69CrossRefPubMedGoogle Scholar
  159. Sugimoto H, Sugahara M, Fölsch H, Koide Y, Nakatsu F, Tanaka N, Nishimura T, Furukawa M, Mullins C, Nakamura N et al (2002) Differential recognition of tyrosine-based basolateral signals by AP-1B subunit mu1B in polarized epithelial cells. Mol Biol Cell 13:2374–2382CrossRefPubMedGoogle Scholar
  160. Sun Y, Ling K, Wagoner MP, Anderson RA (2007) Type I gamma phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration. J Cell Biol 178:297–308CrossRefPubMedGoogle Scholar
  161. Suriano G, Mulholland D, De Wever O, Ferreira P, Mateus A, Bruyneel E, Nelson C, Mareel M, Yokota J, Huntsman D, Seruca R (2003) The intracellular E-cadherin germline mutation V832 M lacks the ability to mediate cell-cell adhesion and to suppress invasion. Oncogene 22:5716–5719CrossRefPubMedGoogle Scholar
  162. Takenawa T, Itoh T (2001) Phosphoinositides, key molecules for regulation of actin cytoskeletal organization and membrane traffic from the plasma membrane. Biochim Biophys Acta 1533:190–206CrossRefPubMedGoogle Scholar
  163. Tall EG, Spector I, Pentyala SN, Bitter I, Rebecchi MJ (2000) Dynamics of phosphatidylinositol 4,5-bisphosphate in actin-rich structures. Curr Biol 10:743–746CrossRefPubMedGoogle Scholar
  164. Tayeb MA, Skalski M, Cha MC, Kean MJ, Scaife M, Coppolino MG (2005) Inhibition of SNARE-mediated membrane traffic impairs cell migration. Exp Cell Res 305:63–73CrossRefPubMedGoogle Scholar
  165. Taylor SS, Knighton DR, Zheng J, Ten Eyck LF, Sowadski JM (1992) Structural framework for the protein kinase family. Annu Rev Cell Biol 8:429–462CrossRefPubMedGoogle Scholar
  166. Taylor SS, Radzio-Andzelm E, Knighton DR, Ten Eyck LF, Sowadski JM, Herberg FW, Yonemoto W, Zheng J (1993) Crystal structures of the catalytic subunit of cAMP-dependent protein kinase reveal general features of the protein kinase family. Receptor 3:165–172PubMedGoogle Scholar
  167. Thieman JR, Mishra SK, Ling K, Doray B, Anderson RA, Traub LM (2009) Clathrin regulates the association of PIPKIgamma661 with the AP-2 adaptor beta2 appendage. J Biol Chem 284:13924–13939CrossRefPubMedGoogle Scholar
  168. Thompson LJ, Fields AP (1996) betaII protein kinase C is required for the G2/M phase transition of cell cycle. J Biol Chem 271:15045–15053CrossRefPubMedGoogle Scholar
  169. Tolias KF, Couvillon AD, Cantley LC, Carpenter CL (1998) Characterization of a Rac1- and RhoGDI-associated lipid kinase signaling complex. Mol Cell Biol 18:762–770PubMedGoogle Scholar
  170. Tolias KF, Hartwig JH, Ishihara H, Shibasaki Y, Cantley LC, Carpenter CL (2000) Type Ialpha phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly. Curr Biol 10:153–156CrossRefPubMedGoogle Scholar
  171. Van Horck FP, Lavazais E, Eickholt BJ, Moolenaar WH, Divecha N (2002) Essential role of type I(alpha) phosphatidylinositol 4-phosphate 5-kinase in neurite remodeling. Curr Biol 12:241–245CrossRefPubMedGoogle Scholar
  172. Van Rheenen J, Song X, Van Roosmalen W, Cammer M, Chen X, Desmarais V, Yip SC, Backer JM, Eddy RJ, Condeelis JS (2007) EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells. J Cell Biol 179:1247–1259CrossRefPubMedGoogle Scholar
  173. Vann LR, Wooding FB, Irvine RF, Divecha N (1997) Metabolism and possible compartmentalization of inositol lipids in isolated rat-liver nuclei. Biochem J 327(Pt 2):569–576PubMedGoogle Scholar
  174. Webb DJ, Parsons JT, Horwitz AF (2002) Adhesion assembly, disassembly and turnover in migrating cells—over and over and over again. Nat Cell Biol 4:E97–E100CrossRefPubMedGoogle Scholar
  175. Weernink PA, Meletiadis K, Hommeltenberg S, Hinz M, Ishihara H, Schmidt M, Jakobs KH (2004) Activation of type I phosphatidylinositol 4-phosphate 5-kinase isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42. J Biol Chem 279:7840–7849CrossRefPubMedGoogle Scholar
  176. Wenk MR, De Camilli P (2004) Protein-lipid interactions and phosphoinositide metabolism in membrane traffic: insights from vesicle recycling in nerve terminals. Proc Natl Acad Sci U S A 101:8262–8269CrossRefPubMedGoogle Scholar
  177. Wenk MR, Pellegrini L, Klenchin VA, Di Paolo G, Chang S, Daniell L, Arioka M, Martin TF, De Camilli P (2001) PIP kinase Igamma is the major PI(4,5)P(2) synthesizing enzyme at the synapse. Neuron 32:79–88CrossRefPubMedGoogle Scholar
  178. Whitman M, Downes CP, Keeler M, Keller T, Cantley L (1988) Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 332:644–646CrossRefPubMedGoogle Scholar
  179. Yabuta T, Shinmura K, Tani M, Yamaguchi S, Yoshimura K, Katai H, Nakajima T, Mochiki E, Tsujinaka T, Takami M et al (2002) E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer. Int J Cancer 101:434–441CrossRefPubMedGoogle Scholar
  180. Yamamoto A, DeWald DB, Boronenkov IV, Anderson RA, Emr SD, Koshland D (1995) Novel PI(4)P 5-kinase homologue, Fab1p, essential for normal vacuole function and morphology in yeast. Mol Biol Cell 6:525–539PubMedGoogle Scholar
  181. Yamamoto M, Hilgemann DH, Feng S, Bito H, Ishihara H, Shibasaki Y, Yin HL (2001) Phosphatidylinositol 4,5-bisphosphate induces actin stress-fiber formation and inhibits membrane ruffling in CV1 cells. J Cell Biol 152:867–876CrossRefPubMedGoogle Scholar
  182. Yamazaki M, Miyazaki H, Watanabe H, Sasaki T, Maehama T, Frohman MA, Kanaho Y (2002) Phosphatidylinositol 4-phosphate 5-kinase is essential for ROCK-mediated neurite remodeling. J Biol Chem 277:17226–17230CrossRefPubMedGoogle Scholar
  183. Yap A, Crampton M, Hardin J (2007) Making and breaking contacts: the cellular biology of cadherin regulation. Curr Opin Cell Biol 19:508–514CrossRefPubMedGoogle Scholar
  184. Yeaman C, Grindstaff KK, Wright JR, Nelson WJ (2001) Sec6/8 complexes on trans-Golgi network and plasma membrane regulate late stages of exocytosis in mammalian cells. J Cell Biol 155:593–604CrossRefPubMedGoogle Scholar
  185. Yin HL, Janmey PA (2003) Phosphoinositide regulation of the actin cytoskeleton. Annu Rev Physiol 65:761–789CrossRefPubMedGoogle Scholar
  186. Yokogawa T, Nagata S, Nishio Y, Tsutsumi T, Ihara S, Shirai R, Morita K, Umeda M, Shirai Y, Saitoh N, Fukui Y (2000) Evidence that 3’-phosphorylated polyphosphoinositides are generated at the nuclear surface: use of immunostaining technique with monoclonal antibodies specific for PI 3,4-P(2). FEBS Lett 473:222–226CrossRefPubMedGoogle Scholar
  187. Yoshinaga-Ohara N, Takahashi A, Uchiyama T, Sasada M (2002) Spatiotemporal regulation of moesin phosphorylation and rear release by Rho and serine/threonine phosphatase during neutrophil migration. Exp Cell Res 278:112–122CrossRefPubMedGoogle Scholar
  188. Yu H, Fukami K, Watanabe Y, Ozaki C, Takenawa T (1998) Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histone H1. Eur J Biochem 251:281–287CrossRefPubMedGoogle Scholar
  189. Zhang X, Loijens JC, Boronenkov IV, Parker GJ, Norris FA, Chen J, Thum O, Prestwich GD, Majerus PW, Anderson RA (1997) Phosphatidylinositol-4-phosphate 5-kinase isozymes catalyze the synthesis of 3-phosphate-containing phosphatidylinositol signaling molecules. J Biol Chem 272:17756–17761CrossRefPubMedGoogle Scholar
  190. Zhang X, Orlando K, He B, Xi F, Zhang J, Zajac A, Guo W (2008) Membrane association and functional regulation of Sec3 by phospholipids and Cdc42. J Cell Biol 180:145–158CrossRefPubMedGoogle Scholar
  191. Zhao K, Wang W, Rando OJ, Xue Y, Swiderek K, Kuo A, Crabtree GR (1998) Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95:625–636CrossRefPubMedGoogle Scholar
  192. Zheng JH, Knighton DR, Parello J, Taylor SS, Sowadski JM (1991) Crystallization of catalytic subunit of adenosine cyclic monophosphate-dependent protein kinase. Methods Enzymol 200:508–521CrossRefPubMedGoogle Scholar
  193. Zou J, Marjanovic J, Kisseleva MV, Wilson M, Majerus PW (2007) Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis. Proc Natl Acad Sci U S A 104:16834–16839CrossRefPubMedGoogle Scholar
  194. Zovein AC, Luque A, Turlo KA, Hofmann JJ, Yee KM, Becker MS, Fassler R, Mellman I, Lane TF, Iruela-Arispe ML (2010) Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Dev Cell 18:39–51Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Mark Schramp
    • 1
  • Andrew Hedman
    • 2
  • Weimin Li
    • 1
  • Xiaojun Tan
    • 2
  • Richard Anderson
    • 1
    Email author
  1. 1.Department of Pharmacology, School of Medicine and Public Health, 3710 Medical Sciences CenterUniversity of Wisconsin Medical SchoolMadisonUSA
  2. 2.Program in Molecular and Cellular PharmacologyUniversity of Wisconsin-MadisonMadisonUSA

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