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PAR-1 Kinase and Cell Polarity

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Cell Polarity 1

Abstract

PAR-1 kinase was identified as one of the protein products of the par (partition defective) genes essential for the establishment of the anterior-posterior polarity of the Caenorhabditis elegans one-cell embryo. Subsequent studies have revealed the ubiquitous importance of the kinase in regulating cell polarity observed in various biological contexts of many organisms. As a membrane-localized kinase, PAR-1 antagonizes the atypical protein kinase C (aPKC)/PAR-3/PAR-6 complex to establish the mutually exclusive membrane domains along the polarity axis. Based on this asymmetric membrane localization, its kinase activity is utilized to phosphorylate various other target proteins that regulate cellular functions. The major function of PAR-1 is the regulation of microtubule dynamics, of which one of the underlying mechanisms was identified as the microtubule affinity-regulating kinase (MARK) activity in mammalian neurons. In addition, accumulating data have revealed the presence of various kinds of other target proteins involved in the regulation of actin cytoskeleton and protein stability. Although the significant versatility of PAR-1 has made it increasingly difficult to obtain a simple view of its function, the evolutional insight on PAR-1 provides a powerful tool for integrating increasing data on this kinase in the light of cell polarity.

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References

  • Barnes AP, Lilley BN, Pan YA, Plummer LJ, Powell AW, Raines AN, Sanes JR, Polleux F (2007) LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell 129(3):549–563. doi:10.1016/j.cell.2007.03.025

    CAS  PubMed  Google Scholar 

  • Bartolini F, Gundersen GG (2006) Generation of noncentrosomal microtubule arrays. J Cell Sci 119(Pt 20):4155–4163. doi:10.1242/jcs.03227

    CAS  PubMed  Google Scholar 

  • Bayraktar J, Zygmunt D, Carthew RW (2006) Par-1 kinase establishes cell polarity and functions in Notch signaling in the Drosophila embryo. J Cell Sci 119(Pt 4):711–721. doi:10.1242/jcs.02789

    CAS  PubMed  Google Scholar 

  • Beatty A, Morton D, Kemphues K (2010) The C. elegans homolog of Drosophila Lethal giant larvae functions redundantly with PAR-2 to maintain polarity in the early embryo. Development 137(23):3995–4004. doi:10.1242/dev.056028

    PubMed Central  CAS  PubMed  Google Scholar 

  • Benton R, St Johnston D (2003) Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells. Cell 115(6):691–704

    CAS  PubMed  Google Scholar 

  • Bernatik O, Ganji RS, Dijksterhuis JP, Konik P, Cervenka I, Polonio T, Krejci P, Schulte G, Bryja V (2011) Sequential activation and inactivation of dishevelled in the Wnt/beta-catenin pathway by casein kinases. J Biol Chem 286(12):10396–10410. doi:10.1074/jbc.M110.169870

    PubMed Central  CAS  PubMed  Google Scholar 

  • Biernat J, Wu YZ, Timm T, Zheng-Fischhofer Q, Mandelkow E, Meijer L, Mandelkow EM (2002) Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity. Mol Biol Cell 13(11):4013–4028. doi:10.1091/mbc.02-03-0046

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bohm H, Brinkmann V, Drab M, Henske A, Kurzchalia TV (1997) Mammalian homologues of C. elegans PAR-1 are asymmetrically localized in epithelial cells and may influence their polarity. Curr Biol 7(8):603–606

    CAS  PubMed  Google Scholar 

  • Brandt R (1996) The tau proteins in neuronal growth and development. Front Biosci 1:d118–d130

    CAS  PubMed  Google Scholar 

  • Chen YM, Wang QJ, Hu HS, Yu PC, Zhu J, Drewes G, Piwnica-Worms H, Luo ZG (2006) Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity. Proc Natl Acad Sci U S A 103(22):8534–8539. doi:10.1073/pnas.0509955103

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chien SC, Brinkmann EM, Teuliere J, Garriga G (2013) Caenorhabditis elegans PIG-1/MELK acts in a conserved PAR-4/LKB1 polarity pathway to promote asymmetric neuroblast divisions. Genetics 193(3):897–909. doi:10.1534/genetics.112.148106

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cohen D, Brennwald PJ, Rodriguez-Boulan E, Musch A (2004) Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton. J Cell Biol 164(5):717–727. doi:10.1083/jcb.200308104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cohen D, Fernandez D, Lazaro-Dieguez F, Musch A (2011) The serine/threonine kinase Par1b regulates epithelial lumen polarity via IRSp53-mediated cell-ECM signaling. J Cell Biol 192(3):525–540. doi:10.1083/jcb.201007002

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cox DN, Lu B, Sun TQ, Williams LT, Jan YN (2001) Drosophila par-1 is required for oocyte differentiation and microtubule organization. Curr Biol 11(2):75–87

    CAS  PubMed  Google Scholar 

  • Daley WP, Gervais EM, Centanni SW, Gulfo KM, Nelson DA, Larsen M (2012) ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity. Development 139(2):411–422. doi:10.1242/dev.075366

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dequiedt F, Martin M, Von Blume J, Vertommen D, Lecomte E, Mari N, Heinen MF, Bachmann M, Twizere JC, Huang MC, Rider MH, Piwnica-Worms H, Seufferlein T, Kettmann R (2006) New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases. Mol Cell Biol 26(19):7086–7102. doi:10.1128/MCB. 00231-06

    PubMed Central  CAS  PubMed  Google Scholar 

  • Doerflinger H, Benton R, Shulman JM, St Johnston D (2003) The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium. Development 130(17):3965–3975

    CAS  PubMed  Google Scholar 

  • Doerflinger H, Benton R, Torres IL, Zwart MF, St Johnston D (2006) Drosophila anterior-posterior polarity requires actin-dependent PAR-1 recruitment to the oocyte posterior. Curr Biol 16(11):1090–1095. doi:10.1016/j.cub.2006.04.001

    CAS  PubMed  Google Scholar 

  • Doerflinger H, Vogt N, Torres IL, Mirouse V, Koch I, Nusslein-Volhard C, St Johnston D (2010) Bazooka is required for polarisation of the Drosophila anterior-posterior axis. Development 137(10):1765–1773. doi:10.1242/dev.045807

    PubMed Central  CAS  PubMed  Google Scholar 

  • Drewes G, Ebneth A, Mandelkow EM (1998) MAPs, MARKs and microtubule dynamics. Trends Biochem Sci 23(8):307–311

    CAS  PubMed  Google Scholar 

  • Drewes G, Ebneth A, Preuss U, Mandelkow EM, Mandelkow E (1997) MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell 89(2):297–308

    CAS  PubMed  Google Scholar 

  • Drewes G, Nurse P (2003) The protein kinase kin1, the fission yeast orthologue of mammalian MARK/PAR-1, localises to new cell ends after mitosis and is important for bipolar growth. FEBS Lett 554(1–2):45–49

    CAS  PubMed  Google Scholar 

  • Ducharme NA, Hales CM, Lapierre LA, Ham AJ, Oztan A, Apodaca G, Goldenring JR (2006) MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells. Mol Biol Cell 17(8):3625–3637. doi:10.1091/mbc.E05-08-0736

    PubMed Central  CAS  PubMed  Google Scholar 

  • Elbert M, Cohen D, Musch A (2006) PAR1b promotes cell-cell adhesion and inhibits dishevelled-mediated transformation of Madin-Darby canine kidney cells. Mol Biol Cell 17(8):3345–3355. doi:10.1091/mbc.E06-03-0193

    PubMed Central  CAS  PubMed  Google Scholar 

  • Etemad-Moghadam B, Guo S, Kemphues KJ (1995) Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos. Cell 83(5):743–752

    CAS  PubMed  Google Scholar 

  • Fu A, Screaton RA (2008) Using kinomics to delineate signaling pathways: control of CRTC2/TORC2 by the AMPK family. Cell Cycle 7(24):3823–3828

    CAS  PubMed  Google Scholar 

  • Griffin EE, Odde DJ, Seydoux G (2011) Regulation of the MEX-5 gradient by a spatially segregated kinase/phosphatase cycle. Cell 146(6):955–968. doi:10.1016/j.cell.2011.08.012

    PubMed Central  CAS  PubMed  Google Scholar 

  • Guo S, Kemphues KJ (1995) par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81(4):611–620

    CAS  PubMed  Google Scholar 

  • Guo S, Kemphues KJ (1996a) Molecular genetics of asymmetric cleavage in the early Caenorhabditis elegans embryo. Curr Opin Genet Dev 6(4):408–415

    CAS  PubMed  Google Scholar 

  • Guo S, Kemphues KJ (1996b) A non-muscle myosin required for embryonic polarity in Caenorhabditis elegans. Nature 382(6590):455–458

    CAS  PubMed  Google Scholar 

  • Hayashi K, Suzuki A, Hirai S, Kurihara Y, Hoogenraad CC, Ohno S (2011a) Maintenance of dendritic spine morphology by partitioning-defective 1b through regulation of microtubule growth. J Neurosci 31(34):12094–12103. doi:10.1523/JNEUROSCI. 0751-11.2011

    CAS  PubMed  Google Scholar 

  • Hayashi K, Suzuki A, Ohno S (2011b) A novel function of the cell polarity-regulating kinase PAR-1/MARK in dendritic spines. Bioarchitecture 1(6):261–266. doi:10.4161/bioa.1.6.19199

    PubMed Central  PubMed  Google Scholar 

  • Hayashi K, Suzuki A, Ohno S (2012) PAR-1/MARK: a kinase essential for maintaining the dynamic state of microtubules. Cell Struct Funct 37(1):21–25

    CAS  PubMed  Google Scholar 

  • Horiguchi K, Hanada T, Fukui Y, Chishti AH (2006) Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity. J Cell Biol 174(3):425–436. doi:10.1083/jcb.200604031

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hurd DD, Kemphues KJ (2003) PAR-1 is required for morphogenesis of the Caenorhabditis elegans vulva. Dev Biol 253(1):54–65

    CAS  PubMed  Google Scholar 

  • Hurov JB, Huang M, White LS, Lennerz J, Choi CS, Cho YR, Kim HJ, Prior JL, Piwnica-Worms D, Cantley LC, Kim JK, Shulman GI, Piwnica-Worms H (2007) Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo. Proc Natl Acad Sci U S A 104(13):5680–5685. doi:10.1073/pnas.0701179104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hurov JB, Stappenbeck TS, Zmasek CM, White LS, Ranganath SH, Russell JH, Chan AC, Murphy KM, Piwnica-Worms H (2001) Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase. Mol Cell Biol 21(9):3206–3219. doi:10.1128/MCB. 21.9.3206-3219.2001

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hurov JB, Watkins JL, Piwnica-Worms H (2004) Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr Biol 14(8):736–741. doi:10.1016/j.cub.2004.04.007

    CAS  PubMed  Google Scholar 

  • Huynh JR, Shulman JM, Benton R, St Johnston D (2001) PAR-1 is required for the maintenance of oocyte fate in Drosophila. Development 128(7):1201–1209

    CAS  PubMed  Google Scholar 

  • Izumi Y, Hirose T, Tamai Y, Hirai S, Nagashima Y, Fujimoto T, Tabuse Y, Kemphues KJ, Ohno S (1998) An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. J Cell Biol 143(1):95–106

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jaworski J, Kapitein LC, Gouveia SM, Dortland BR, Wulf PS, Grigoriev I, Camera P, Spangler SA, Di Stefano P, Demmers J, Krugers H, Defilippi P, Akhmanova A, Hoogenraad CC (2009) Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity. Neuron 61(1):85–100. doi:10.1016/j.neuron.2008.11.013

    CAS  PubMed  Google Scholar 

  • Kemphues KJ, Priess JR, Morton DG, Cheng NS (1988) Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52(3):311–320

    CAS  PubMed  Google Scholar 

  • Knust E, Bossinger O (2002) Composition and formation of intercellular junctions in epithelial cells. Science 298(5600):1955–1959. doi:10.1126/science.1072161

    CAS  PubMed  Google Scholar 

  • Kusakabe M, Nishida E (2004) The polarity-inducing kinase Par-1 controls Xenopus gastrulation in cooperation with 14-3-3 and aPKC. EMBO J 23(21):4190–4201. doi:10.1038/sj.emboj.7600381

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lee JH, Koh H, Kim M, Kim Y, Lee SY, Karess RE, Lee SH, Shong M, Kim JM, Kim J, Chung J (2007) Energy-dependent regulation of cell structure by AMP-activated protein kinase. Nature 447(7147):1017–1020. doi:10.1038/nature05828

    CAS  PubMed  Google Scholar 

  • Lennerz JK, Hurov JB, White LS, Lewandowski KT, Prior JL, Planer GJ, Gereau RW, Piwnica-Worms D, Schmidt RE, Piwnica-Worms H (2010) Loss of Par-1a/MARK3/C-TAK1 kinase leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis. Mol Cell Biol 30(21):5043–5056. doi:10.1128/MCB. 01472-09

    PubMed Central  CAS  PubMed  Google Scholar 

  • Levin DE, Bishop JM (1990) A putative protein kinase gene (kin1+) is important for growth polarity in Schizosaccharomyces pombe. Proc Natl Acad Sci U S A 87(21):8272–8276

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lizcano JM, Goransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Makela TP, Hardie DG, Alessi DR (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J 23(4):833–843. doi:10.1038/sj.emboj.7600110

    PubMed Central  CAS  PubMed  Google Scholar 

  • Majumder P, Aranjuez G, Amick J, McDonald JA (2012) Par-1 controls myosin-II activity through myosin phosphatase to regulate border cell migration. Curr Biol 22(5):363–372. doi:10.1016/j.cub.2012.01.037

    PubMed Central  CAS  PubMed  Google Scholar 

  • Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298(5600):1912–1934. doi:10.1126/science.1075762

    CAS  PubMed  Google Scholar 

  • Marx A, Nugoor C, Muller J, Panneerselvam S, Timm T, Bilang M, Mylonas E, Svergun DI, Mandelkow EM, Mandelkow E (2006) Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2. J Biol Chem 281(37):27586–27599. doi:10.1074/jbc.M604865200

    CAS  PubMed  Google Scholar 

  • Marx A, Nugoor C, Panneerselvam S, Mandelkow E (2010) Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases. FASEB J 24(6):1637–1648. doi:10.1096/fj.09-148064

    CAS  PubMed  Google Scholar 

  • Masuda-Hirata M, Suzuki A, Amano Y, Yamashita K, Ide M, Yamanaka T, Sakai M, Imamura M, Ohno S (2009) Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex. Genes Cells 14(7):835–850. doi:10.1111/j.1365-2443.2009.01315.x

    CAS  PubMed  Google Scholar 

  • Matenia D, Griesshaber B, Li XY, Thiessen A, Johne C, Jiao J, Mandelkow E, Mandelkow EM (2005) PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable microtubules and dynamic actin. Mol Biol Cell 16(9):4410–4422. doi:10.1091/mbc.E05-01-0081

    PubMed Central  CAS  PubMed  Google Scholar 

  • Matenia D, Mandelkow EM (2009) The tau of MARK: a polarized view of the cytoskeleton. Trends Biochem Sci 34(7):332–342. doi:10.1016/j.tibs.2009.03.008

    CAS  PubMed  Google Scholar 

  • Matsubayashi H, Sese S, Lee JS, Shirakawa T, Iwatsubo T, Tomita T, Yanagawa S (2004) Biochemical characterization of the Drosophila wingless signaling pathway based on RNA interference. Mol Cell Biol 24(5):2012–2024

    PubMed Central  CAS  PubMed  Google Scholar 

  • McKinley RF, Harris TJ (2012) Displacement of basolateral Bazooka/PAR-3 by regulated transport and dispersion during epithelial polarization in Drosophila. Mol Biol Cell 23(22):4465–4471. doi:10.1091/mbc.E12-09-0655

    PubMed Central  CAS  PubMed  Google Scholar 

  • Morais-de-Sa E, Vega-Rioja A, Trovisco V, St Johnston D (2013) Oskar is targeted for degradation by the sequential action of Par-1, GSK-3, and the SCF(-Slimb) ubiquitin ligase. Dev Cell 26(3):303–314. doi:10.1016/j.devcel.2013.06.011

    PubMed Central  CAS  PubMed  Google Scholar 

  • Moravcevic K, Mendrola JM, Schmitz KR, Wang YH, Slochower D, Janmey PA, Lemmon MA (2010) Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids. Cell 143(6):966–977. doi:10.1016/j.cell.2010.11.028

    PubMed Central  CAS  PubMed  Google Scholar 

  • Motegi F, Zonies S, Hao Y, Cuenca AA, Griffin E, Seydoux G (2011) Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes. Nat Cell Biol 13(11):1361–1367. doi:10.1038/ncb2354

    PubMed Central  CAS  PubMed  Google Scholar 

  • Muller J, Ritt DA, Copeland TD, Morrison DK (2003) Functional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate. EMBO J 22(17):4431–4442. doi:10.1093/emboj/cdg426

    PubMed Central  PubMed  Google Scholar 

  • Munro E, Nance J, Priess JR (2004) Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev Cell 7(3):413–424. doi:10.1016/j.devcel.2004.08.001

    CAS  PubMed  Google Scholar 

  • Murphy JM, Korzhnev DM, Ceccarelli DF, Briant DJ, Zarrine-Afsar A, Sicheri F, Kay LE, Pawson T (2007) Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain. Proc Natl Acad Sci U S A 104(36):14336–14341. doi:10.1073/pnas.0703012104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nesic D, Miller MC, Quinkert ZT, Stein M, Chait BT, Stebbins CE (2010) Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates. Nat Struct Mol Biol 17(1):130–132. doi:10.1038/nsmb.1705

    CAS  PubMed  Google Scholar 

  • Nishimura T, Kato K, Yamaguchi T, Fukata Y, Ohno S, Kaibuchi K (2004) Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity. Nat Cell Biol 6(4):328–334. doi:10.1038/ncb1118

    CAS  PubMed  Google Scholar 

  • Ossipova O, Dhawan S, Sokol S, Green JB (2005) Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development. Dev Cell 8(6):829–841. doi:10.1016/j.devcel.2005.04.011

    CAS  PubMed  Google Scholar 

  • Ossipova O, Ezan J, Sokol SY (2009) PAR-1 phosphorylates mind bomb to promote vertebrate neurogenesis. Dev Cell 17(2):222–233. doi:10.1016/j.devcel.2009.06.010

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ossipova O, Sokol SY (2011) Neural crest specification by noncanonical Wnt signaling and PAR-1. Development 138(24):5441–5450. doi:10.1242/dev.067280

    PubMed Central  CAS  PubMed  Google Scholar 

  • Panneerselvam S, Marx A, Mandelkow EM, Mandelkow E (2006) Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1. Structure 14(2):173–183. doi:10.1016/j.str.2005.09.022

    CAS  PubMed  Google Scholar 

  • Parton RM, Hamilton RS, Ball G, Yang L, Cullen CF, Lu W, Ohkura H, Davis I (2011) A PAR-1-dependent orientation gradient of dynamic microtubules directs posterior cargo transport in the Drosophila oocyte. J Cell Biol 194(1):121–135. doi:10.1083/jcb.201103160

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pellettieri J, Seydoux G (2002) Anterior-posterior polarity in C. elegans and Drosophila–PARallels and differences. Science 298(5600):1946–1950. doi:10.1126/science.1072162

    CAS  PubMed  Google Scholar 

  • Peng CY, Graves PR, Ogg S, Thoma RS, Byrnes MJ 3rd, Wu Z, Stephenson MT, Piwnica-Worms H (1998) C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. Cell Growth Differ 9(3):197–208

    CAS  PubMed  Google Scholar 

  • Riechmann V, Ephrussi A (2001) Axis formation during Drosophila oogenesis. Curr Opin Genet Dev 11(4):374–383

    CAS  PubMed  Google Scholar 

  • Riechmann V, Ephrussi A (2004) Par-1 regulates bicoid mRNA localisation by phosphorylating Exuperantia. Development 131(23):5897–5907. doi:10.1242/dev.01515

    CAS  PubMed  Google Scholar 

  • Riechmann V, Gutierrez GJ, Filardo P, Nebreda AR, Ephrussi A (2002) Par-1 regulates stability of the posterior determinant Oskar by phosphorylation. Nat Cell Biol 4(5):337–342. doi:10.1038/ncb782

    CAS  PubMed  Google Scholar 

  • Sapir T, Sapoznik S, Levy T, Finkelshtein D, Shmueli A, Timm T, Mandelkow EM, Reiner O (2008) Accurate balance of the polarity kinase MARK2/Par-1 is required for proper cortical neuronal migration. J Neurosci 28(22):5710–5720. doi:10.1523/jneurosci. 0911-08.2008

    CAS  PubMed  Google Scholar 

  • Sato Y, Akitsu M, Amano Y, Yamashita K, Ide M, Shimada K, Yamashita A, Hirano H, Arakawa N, Maki T, Hayashi I, Ohno S, Suzuki A (2013) The novel PAR-1-binding protein MTCL1 has crucial roles in organizing microtubules in polarizing epithelial cells. J Cell Sci 126(Pt 20):4671–4683. doi:10.1242/jcs.127845

    CAS  PubMed  Google Scholar 

  • Schaar BT, Kinoshita K, McConnell SK (2004) Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons. Neuron 41(2):203–213

    CAS  PubMed  Google Scholar 

  • Shi SH, Jan LY, Jan YN (2003) Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 112(1):63–75

    CAS  PubMed  Google Scholar 

  • Shulman JM, Benton R, St Johnston D (2000) The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole. Cell 101(4):377–388

    CAS  PubMed  Google Scholar 

  • Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT (2001) PAR-1 is a dishevelled-associated kinase and a positive regulator of Wnt signalling. Nat Cell Biol 3(7):628–636. doi:10.1038/35083016

    CAS  PubMed  Google Scholar 

  • Sung HH, Telley IA, Papadaki P, Ephrussi A, Surrey T, Rorth P (2008) Drosophila ensconsin promotes productive recruitment of Kinesin-1 to microtubules. Dev Cell 15(6):866–876. doi:10.1016/j.devcel.2008.10.006

    CAS  PubMed  Google Scholar 

  • Suzuki A, Hirata M, Kamimura K, Maniwa R, Yamanaka T, Mizuno K, Kishikawa M, Hirose H, Amano Y, Izumi N, Miwa Y, Ohno S (2004) aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity. Curr Biol 14(16):1425–1435. doi:10.1016/j.cub.2004.08.021

    CAS  PubMed  Google Scholar 

  • Suzuki A, Ohno S (2006) The PAR-aPKC system: lessons in polarity. J Cell Sci 119(Pt 6):979–987. doi:10.1242/jcs.02898

    CAS  PubMed  Google Scholar 

  • Tabuse Y, Izumi Y, Piano F, Kemphues KJ, Miwa J, Ohno S (1998) Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans. Development 125(18):3607–3614

    CAS  PubMed  Google Scholar 

  • Tanaka E, Ho T, Kirschner MW (1995) The role of microtubule dynamics in growth cone motility and axonal growth. J Cell Biol 128(1–2):139–155

    CAS  PubMed  Google Scholar 

  • Tassan JP, Le Goff X (2004) An overview of the KIN1/PAR-1/MARK kinase family. Biol Cell 96(3):193–199. doi:10.1016/j.biolcel.2003.10.009

    CAS  PubMed  Google Scholar 

  • Terabayashi T, Funato Y, Miki H (2008) Dishevelled-induced phosphorylation regulates membrane localization of Par1b. Biochem Biophys Res Commun 375(4):660–665. doi:10.1016/j.bbrc.2008.08.098

    CAS  PubMed  Google Scholar 

  • Terabayashi T, Itoh TJ, Yamaguchi H, Yoshimura Y, Funato Y, Ohno S, Miki H (2007) Polarity-regulating kinase partitioning-defective 1/microtubule affinity-regulating kinase 2 negatively regulates development of dendrites on hippocampal neurons. J Neurosci 27(48):13098–13107. doi:10.1523/JNEUROSCI. 3986-07.2007

    CAS  PubMed  Google Scholar 

  • Tian AG, Deng WM (2008) Lgl and its phosphorylation by aPKC regulate oocyte polarity formation in Drosophila. Development 135(3):463–471. doi:10.1242/dev.016253

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tian AG, Deng WM (2009) Par-1 and Tau regulate the anterior-posterior gradient of microtubules in Drosophila oocytes. Dev Biol 327(2):458–464. doi:10.1016/j.ydbio.2008.12.031

    PubMed Central  CAS  PubMed  Google Scholar 

  • Timm T, Balusamy K, Li X, Biernat J, Mandelkow E, Mandelkow EM (2008a) Glycogen synthase kinase (GSK) 3beta directly phosphorylates Serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2. J Biol Chem 283(27):18873–18882. doi:10.1074/jbc.M706596200

    CAS  PubMed  Google Scholar 

  • Timm T, Li XY, Biernat J, Jiao J, Mandelkow E, Vandekerckhove J, Mandelkow EM (2003) MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1. EMBO J 22(19):5090–5101. doi:10.1093/emboj/cdg447

    PubMed Central  CAS  PubMed  Google Scholar 

  • Timm T, Marx A, Panneerselvam S, Mandelkow E, Mandelkow EM (2008b) Structure and regulation of MARK, a kinase involved in abnormal phosphorylation of Tau protein. BMC Neurosci 9(Suppl 2):9. doi:10.1186/1471-2202-9-S2-S9

    Google Scholar 

  • Timm T, von Kries JP, Li X, Zempel H, Mandelkow E, Mandelkow EM (2011) Microtubule affinity regulating kinase activity in living neurons was examined by a genetically encoded fluorescence resonance energy transfer/fluorescence lifetime imaging-based biosensor: inhibitors with therapeutic potential. J Biol Chem 286(48):41711–41722. doi:10.1074/jbc.M111.257865

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tochio N, Koshiba S, Kobayashi N, Inoue M, Yabuki T, Aoki M, Seki E, Matsuda T, Tomo Y, Motoda Y, Kobayashi A, Tanaka A, Hayashizaki Y, Terada T, Shirouzu M, Kigawa T, Yokoyama S (2006) Solution structure of the kinase-associated domain 1 of mouse microtubule-associated protein/microtubule affinity-regulating kinase 3. Protein Sci 15(11):2534–2543. doi:10.1110/ps.062391106

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tzivion G, Shen YH, Zhu J (2001) 14-3-3 proteins; bringing new definitions to scaffolding. Oncogene 20(44):6331–6338. doi:10.1038/sj.onc.1204777

    CAS  PubMed  Google Scholar 

  • Uboha NV, Flajolet M, Nairn AC, Picciotto MR (2007) A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity regulating kinase 2 signaling cascade mediates calcium-dependent neurite outgrowth. J Neurosci 27(16):4413–4423. doi:10.1523/JNEUROSCI. 0725-07.2007

    CAS  PubMed  Google Scholar 

  • Vaccari T, Ephrussi A (2002) The fusome and microtubules enrich Par-1 in the oocyte, where it effects polarization in conjunction with Par-3, BicD, Egl, and dynein. Curr Biol 12(17):1524–1528

    CAS  PubMed  Google Scholar 

  • Wang YC, Khan Z, Kaschube M, Wieschaus EF (2012) Differential positioning of adherens junctions is associated with initiation of epithelial folding. Nature 484(7394):390–393. doi:10.1038/nature10938

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wu JC, Rose LS (2007) PAR-3 and PAR-1 inhibit LET-99 localization to generate a cortical band important for spindle positioning in Caenorhabditis elegans embryos. Mol Biol Cell 18(11):4470–4482. doi:10.1091/mbc.E07-02-0105

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wu Q, DiBona VL, Bernard LP, Zhang H (2012) The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95). J Biol Chem 287(36):30781–30788. doi:10.1074/jbc.M112.351452

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yamahashi Y, Saito Y, Murata-Kamiya N, Hatakeyama M (2011) Polarity-regulating kinase partitioning-defective 1b (PAR1b) phosphorylates guanine nucleotide exchange factor H1 (GEF-H1) to regulate RhoA-dependent actin cytoskeletal reorganization. J Biol Chem 286(52):44576–44584. doi:10.1074/jbc.M111.267021

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yamashita K, Suzuki A, Satoh Y, Ide M, Amano Y, Masuda-Hirata M, Hayashi YK, Hamada K, Ogata K, Ohno S (2010) The 8th and 9th tandem spectrin-like repeats of utrophin cooperatively form a functional unit to interact with polarity-regulating kinase PAR-1b. Biochem Biophys Res Commun 391(1):812–817. doi:10.1016/j.bbrc.2009.11.144

    CAS  PubMed  Google Scholar 

  • Yoshimura Y, Miki H (2011) Dynamic regulation of GEF-H1 localization at microtubules by Par1b/MARK2. Biochem Biophys Res Commun 408(2):322–328. doi:10.1016/j.bbrc.2011.04.032

    CAS  PubMed  Google Scholar 

  • Yoshimura Y, Terabayashi T, Miki H (2010) Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation. Mol Cell Biol 30(9):2206–2219. doi:10.1128/MCB. 01181-09

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zagorska A, Deak M, Campbell DG, Banerjee S, Hirano M, Aizawa S, Prescott AR, Alessi DR (2010) New roles for the LKB1-NUAK pathway in controlling myosin phosphatase complexes and cell adhesion. Sci Signal 3(115):ra25. doi:10.1126/scisignal.2000616

    PubMed  Google Scholar 

  • Zhang SH, Kobayashi R, Graves PR, Piwnica-Worms H, Tonks NK (1997) Serine phosphorylation-dependent association of the band 4.1-related protein-tyrosine phosphatase PTPH1 with 14-3-3beta protein. J Biol Chem 272(43):27281–27287

    CAS  PubMed  Google Scholar 

  • Zhang X, Zhu J, Yang GY, Wang QJ, Qian L, Chen YM, Chen F, Tao Y, Hu HS, Wang T, Luo ZG (2007a) Dishevelled promotes axon differentiation by regulating atypical protein kinase C. Nat Cell Biol 9(7):743–754. doi:10.1038/ncb1603

    CAS  PubMed  Google Scholar 

  • Zhang Y, Guo H, Kwan H, Wang JW, Kosek J, Lu B (2007b) PAR-1 kinase phosphorylates and regulates its postsynaptic targeting at the Drosophila neuromuscular junction. Neuron 53(2):201–215. doi:10.1016/j.neuron.2006.12.016

    PubMed Central  CAS  PubMed  Google Scholar 

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  1. Molecular Cellular Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi, Yokohama, 230-0045, Japan

    Atsushi Suzuki

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  1. Atsushi Suzuki
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  1. Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation (ZMBE), University Münster, Münster, Nordrhein-Westfalen, Germany

    Klaus Ebnet

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Suzuki, A. (2015). PAR-1 Kinase and Cell Polarity. In: Ebnet, K. (eds) Cell Polarity 1. Springer, Cham. https://doi.org/10.1007/978-3-319-14463-4_2

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