Genomes and Genes
Gene Symbol: par-1
Alias: 27C1, BcDNA:RH48823, CG11960, CG16701, CG30131, CG30132, CG8201, DPAR-1, DPar1, Dmel\CG8201, EMK, MARK, PAR-1, PAR1, PAR1/MARK2, Par-1, Par1, anon-WO0210402.19, dMARK, dPAR-1, dPAR1, dPar-1, dPar1, l(2)27C1, l(2)k06323, par1, par-1, C-TAK1-like, CG8201-PA, CG8201-PH, CG8201-PL, CG8201-PP, CG8201-PQ, CG8201-PR, CG8201-PS, CG8201-PT, CG8201-PV, CG8201-PW, CG8201-PX, ELKL motif kinase, Par-1 kinase, Par-1 protein kinase, lethal (2) 27C1, par-1-PA, par-1-PH, par-1-PL, par-1-PP, par-1-PQ, par-1-PR, par-1-PS, par-1-PT, par-1-PV, par-1-PW, par-1-PX, partitioning defective-1
Species: fruit fly
- Kemphues K. PARsing embryonic polarity. Cell. 2000;101:345-8 pubmed
- Shulman J, Benton R, St Johnston D. The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole. Cell. 2000;101:377-88 pubmed..These results identify a molecular parallel between anterior-posterior polarization in Drosophila and C. elegans. ..
- Iijima Ando K, Zhao L, Gatt A, Shenton C, Iijima K. A DNA damage-activated checkpoint kinase phosphorylates tau and enhances tau-induced neurodegeneration. Hum Mol Genet. 2010;19:1930-8 pubmed publisher..Since accumulation of DNA damage has been detected in the brains of AD patients, our results suggest that the DNA damage-activated kinases Chk1 and Chk2 may be involved in tau phosphorylation and toxicity in the pathogenesis of AD. ..
- Benton R, St Johnston D. Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells. Cell. 2003;115:691-704 pubmed..Thus, antagonism of Bazooka by PAR-1/14-3-3 may represent a general mechanism for establishing complementary cortical domains in polarized cells. ..
- Wang Y, Khan Z, Kaschube M, Wieschaus E. Differential positioning of adherens junctions is associated with initiation of epithelial folding. Nature. 2012;484:390-3 pubmed publisher..Our data thus establish a direct link between modification of epithelial polarity and initiation of epithelial folding...
- Bayraktar J, Zygmunt D, Carthew R. Par-1 kinase establishes cell polarity and functions in Notch signaling in the Drosophila embryo. J Cell Sci. 2006;119:711-21 pubmed..Epistasis analysis indicates that Par-1 functions upstream of Notch and is critical for proper localization of the Notch ligand Delta. ..
- Sanghavi P, Lu S, Gonsalvez G. A functional link between localized Oskar, dynamic microtubules, and endocytosis. Dev Biol. 2012;367:66-77 pubmed publisher..Thus, multiple polarity-determining pathways are functionally linked in the Drosophila oocytes. ..
- Pellettieri J, Seydoux G. Anterior-posterior polarity in C. elegans and Drosophila--PARallels and differences. Science. 2002;298:1946-50 pubmed..Although clear mechanistic parallels remain to be established, par-dependent regulation of microtubule dynamics and protein stability emerge as common themes. ..
- Vaccari T, Ephrussi A. 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. 2002;12:1524-8 pubmed
- Riechmann V, Gutierrez G, Filardo P, Nebreda A, Ephrussi A. Par-1 regulates stability of the posterior determinant Oskar by phosphorylation. Nat Cell Biol. 2002;4:337-42 pubmed..We show in cell-free extracts that Osk protein is intrinsically unstable and that it is stabilized after phosphorylation by Par-1. Our data indicate that posteriorly localized Par-1 regulates posterior patterning by stabilizing Osk. ..
- Tomancak P, Piano F, Riechmann V, Gunsalus K, Kemphues K, Ephrussi A. A Drosophila melanogaster homologue of Caenorhabditis elegans par-1 acts at an early step in embryonic-axis formation. Nat Cell Biol. 2000;2:458-60 pubmed
- Majumder P, Aranjuez G, Amick J, McDonald J. Par-1 controls myosin-II activity through myosin phosphatase to regulate border cell migration. Curr Biol. 2012;22:363-72 pubmed publisher..We further demonstrate that the cell polarity protein Par-1 (MARK), a serine-threonine kinase, regulates the localization and activation of Myo-II in border cells...
- Doerflinger H, Benton R, Shulman J, St Johnston D. The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium. Development. 2003;130:3965-75 pubmed..Although the direct targets of PAR-1 are unknown, we suggest that it functions by regulating the plus ends, possibly by capping them at the basal cortex. ..
- Zhang Y, Guo H, Kwan H, Wang J, Kosek J, Lu B. PAR-1 kinase phosphorylates Dlg and regulates its postsynaptic targeting at the Drosophila neuromuscular junction. Neuron. 2007;53:201-15 pubmed..Control of Dlg synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical event in synaptogenesis. ..
- Huynh J, Shulman J, Benton R, St Johnston D. PAR-1 is required for the maintenance of oocyte fate in Drosophila. Development. 2001;128:1201-9 pubmed..Finally, we show that PAR-1 localises on the fusome, and provides a link between the asymmetry of the fusome and the selection of the oocyte. ..
- Iijima Ando K, Sekiya M, Maruko Otake A, Ohtake Y, Suzuki E, Lu B, et al. Loss of axonal mitochondria promotes tau-mediated neurodegeneration and Alzheimer's disease-related tau phosphorylation via PAR-1. PLoS Genet. 2012;8:e1002918 pubmed publisher..Our results suggest that loss of axonal mitochondria may play an important role in tau phosphorylation and toxicity in the pathogenesis of AD. ..
- Morais de Sá E, Vega Rioja A, Trovisco V, St Johnston D. Oskar is targeted for degradation by the sequential action of Par-1, GSK-3, and the SCF?Slimb ubiquitin ligase. Dev Cell. 2013;26:303-14 pubmed publisher..These results reveal that Par-1 controls the timing of pole plasm assembly by promoting the localization of oskar mRNA but inhibiting the accumulation of Short Oskar protein. ..
- Amin N, Khan A, St Johnston D, Tomlinson I, Martin S, BRENMAN J, et al. LKB1 regulates polarity remodeling and adherens junction formation in the Drosophila eye. Proc Natl Acad Sci U S A. 2009;106:8941-6 pubmed publisher..These data suggest that in complex tissues, LKB1 acts on an array of targets to regulate cell polarity. ..
- Baas A, Smit L, Clevers H. LKB1 tumor suppressor protein: PARtaker in cell polarity. Trends Cell Biol. 2004;14:312-9 pubmed..In this article, we summarize the findings regarding LKB1 over the past six years. In addition, we discuss LKB1 in polarity in the context of both the other PAR proteins and its tumor suppressive activities. ..
- Lighthouse D, Buszczak M, Spradling A. New components of the Drosophila fusome suggest it plays novel roles in signaling and transport. Dev Biol. 2008;317:59-71 pubmed publisher..In contrast, rab11 is required to maintain the germline stem cells, and to maintain the vesicle content of the spectrosome, suggesting that the fusome mediates intercellular signals that depend on the recycling endosome. ..
- Chen X, Li Y, Huang J, Cao D, Yang G, Liu W, et al. Study of tauopathies by comparing Drosophila and human tau in Drosophila. Cell Tissue Res. 2007;329:169-78 pubmed..These results suggest that the two tau genes differ significantly. This comparison between species-specific isoforms may help to clarify whether the homologous tau genes are conserved. ..
- McDonald J, Khodyakova A, Aranjuez G, Dudley C, Montell D. PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells. Curr Biol. 2008;18:1659-67 pubmed publisher..We identified the Drosophila homolog of the serine/threonine kinase PAR-1 (MARK/Kin1) in a screen for mutations that disrupt border cell migration...
- Doerflinger H, Benton R, Torres I, Zwart M, St Johnston D. Drosophila anterior-posterior polarity requires actin-dependent PAR-1 recruitment to the oocyte posterior. Curr Biol. 2006;16:1090-5 pubmed..Our results therefore identify a molecular parallel between axis formation in Drosophila and C. elegans and make Drosophila PAR-1 N1 the earliest known marker for the polarization of the oocyte. ..
- Parton R, Hamilton R, Ball G, Yang L, Cullen C, Lu W, et al. A PAR-1-dependent orientation gradient of dynamic microtubules directs posterior cargo transport in the Drosophila oocyte. J Cell Biol. 2011;194:121-35 pubmed publisher..Our findings explain the biased random posterior cargo movements in the oocyte that establish the germline and posterior. ..
- Nishimura I, Yang Y, Lu B. PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell. 2004;116:671-82 pubmed..These findings begin to differentiate the effects of various phosphorylation events on tau toxicity and provide potential therapeutic targets. ..
- Doerflinger H, Vogt N, Torres I, Mirouse V, Koch I, NUSSLEIN VOLHARD C, et al. Bazooka is required for polarisation of the Drosophila anterior-posterior axis. Development. 2010;137:1765-73 pubmed publisher..Since non-phosphorylatable Par-1 is epistatic to uninhibitable Baz, Par-1 seems to function downstream of the other PAR proteins to polarize the oocyte microtubule cytoskeleton. ..
- Wang J, Imai Y, Lu B. Activation of PAR-1 kinase and stimulation of tau phosphorylation by diverse signals require the tumor suppressor protein LKB1. J Neurosci. 2007;27:574-81 pubmed..Microtubule affinity regulating kinase (MARK) and PAR-1 have been identified as physiological tau kinases, and aberrant phosphorylation of MARK/PAR-1 target ..
- Huynh J, Petronczki M, Knoblich J, St Johnston D. Bazooka and PAR-6 are required with PAR-1 for the maintenance of oocyte fate in Drosophila. Curr Biol. 2001;11:901-6 pubmed..elegans and Drosophila, the relationships between them are different, as the localization of PAR-1 does not require Bazooka or PAR-6 in Drosophila, as it does in the worm. ..
- Hachet O, Ephrussi A. Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport. Curr Biol. 2001;11:1666-74 pubmed..Our findings indicate that Y14 is part of the oskar mRNA localization complex and that the nuclear shuttling protein Y14 has a specific and direct role in oskar mRNA cytoplasmic localization. ..
- Chatterjee S, Sang T, Lawless G, Jackson G. Dissociation of tau toxicity and phosphorylation: role of GSK-3beta, MARK and Cdk5 in a Drosophila model. Hum Mol Genet. 2009;18:164-77 pubmed publisher..kinase 5 (Cdk5), as well as nonproline-directed kinases such as microtubule affinity-regulating kinase (MARK)/PAR-1; however, whether the cascade of events linking tau phosphorylation and neurodegeneration involves ..
- Wodarz A. Establishing cell polarity in development. Nat Cell Biol. 2002;4:E39-44 pubmed..There is growing evidence that the proteins encoded by these genes interact with key regulators of both the actin and the microtubule cytoskeletons. ..
- Lee S, Wang J, Yu W, Lu B. Phospho-dependent ubiquitination and degradation of PAR-1 regulates synaptic morphology and tau-mediated A? toxicity in Drosophila. Nat Commun. 2012;3:1312 pubmed publisherThe conserved kinases PAR-1/MARK are critically involved in processes such as asymmetric cell division, cell polarity and neuronal differentiation...
- Tian A, Deng W. Lgl and its phosphorylation by aPKC regulate oocyte polarity formation in Drosophila. Development. 2008;135:463-71 pubmed..Our studies suggest that Lgl and its phosphorylation by aPKC may form a conserved regulatory circuitry in polarization of various cell types. ..
- Sun T, Lu B, Feng J, Reinhard C, Jan Y, Fantl W, et al. PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nat Cell Biol. 2001;3:628-36 pubmed..These findings show that PAR-1, a regulator of polarity, is also a modulator of Wnt-beta-catenin signalling, indicating a link between two important developmental pathways. ..
- Benton R, Palacios I, St Johnston D. Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation. Dev Cell. 2002;3:659-71 pubmed..The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries. ..
- Tassan J, Le Goff X. An overview of the KIN1/PAR-1/MARK kinase family. Biol Cell. 2004;96:193-9 pubmedMembers of the KIN1/PAR-1/MARK kinase family are conserved from yeast to humans and share a similar primary structural organization...
- Dahlgaard K, Raposo A, Niccoli T, St Johnston D. Capu and Spire assemble a cytoplasmic actin mesh that maintains microtubule organization in the Drosophila oocyte. Dev Cell. 2007;13:539-53 pubmed..When inactive, unrestrained kinesin movement generates flows that wash microtubules to the cortex. ..
- Martin S, St Johnston D. A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity. Nature. 2003;421:379-84 pubmed..Thus, Drosophila and human LKB1 may be functional homologues, suggesting that loss of cell polarity may contribute to tumour formation in individuals with Peutz-Jeghers syndrome...
- Jia J, Zhang W, Wang B, Trinko R, Jiang J. The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis. Genes Dev. 2003;17:2514-9 pubmed..dMST forms a complex with Sav and Wts, two tumor suppressors also implicated in regulating both cell proliferation and apoptosis, suggesting that they act in common pathways. ..
- Wu P, Tsai P, Chen G, Chou H, Huang Y, Chen Y, et al. DAPK activates MARK1/2 to regulate microtubule assembly, neuronal differentiation, and tau toxicity. Cell Death Differ. 2011;18:1507-20 pubmed publisher..In this study, we report that DAPK inhibits microtubule (MT) assembly by activating MARK/PAR-1 family kinases MARK1/2, which destabilize MT by phosphorylating tau and related MAP2/4...
- Vaccari T, Rabouille C, Ephrussi A. The Drosophila PAR-1 spacer domain is required for lateral membrane association and for polarization of follicular epithelial cells. Curr Biol. 2005;15:255-61 pubmedThe Ser/Thr kinases of the PAR-1/MARK/Kin1 family are conserved regulators of polarity in epithelial and non-epithelial cells ...
- Zimyanin V, Lowe N, St Johnston D. An oskar-dependent positive feedback loop maintains the polarity of the Drosophila oocyte. Curr Biol. 2007;17:353-9 pubmed
- Krahn M, Egger Adam D, Wodarz A. PP2A antagonizes phosphorylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts. Dev Cell. 2009;16:901-8 pubmed publisher..Overexpression of PAR-1 or Baz, or mutation of 14-3-3 proteins that bind phosphorylated Baz, causes essentially the same phenotype, indicating that the balance of PAR-1 and PP2A effects on Baz phosphorylation determines NB polarity. ..
- Yuan H, Chiang C, Cheng J, Salzmann V, Yamashita Y. Regulation of cyclin A localization downstream of Par-1 function is critical for the centrosome orientation checkpoint in Drosophila male germline stem cells. Dev Biol. 2012;361:57-67 pubmed publisher..We propose that the regulation of cyclin A localization via Par-1 function plays a critical role in the centrosome orientation checkpoint. ..
- Venkei Z, Yamashita Y. The centrosome orientation checkpoint is germline stem cell specific and operates prior to the spindle assembly checkpoint in Drosophila testis. Development. 2015;142:62-9 pubmed publisher..This study may provide a framework for identifying and understanding similar mechanisms that might be in place in other asymmetrically dividing cell types. ..
- Simons M, Gault W, Gotthardt D, Rohatgi R, Klein T, Shao Y, et al. Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization. Nat Cell Biol. 2009;11:286-94 pubmed publisher..This stabilization is particularly important for the PCP signalling branch and, thus, promotes specific pathway selection in Wnt signalling. ..
- Lin M, Fan S, Hsu W, Chou T. Drosophila decapping protein 1, dDcp1, is a component of the oskar mRNP complex and directs its posterior localization in the oocyte. Dev Cell. 2006;10:601-13 pubmed..Thus, as well as being a general factor required for mRNA decay, dDcp1 is an essential component of the osk mRNP localization complex. ..
- Januschke J, Gonzalez C. The interphase microtubule aster is a determinant of asymmetric division orientation in Drosophila neuroblasts. J Cell Biol. 2010;188:693-706 pubmed publisher..We have also found that the span of such memory is limited to the last mitosis. Furthermore, the orientation of the NB axis of polarity can be reset to any angle with respect to the surrounding tissue and is, therefore, cell autonomous...
- Matsubayashi H, Sese S, Lee J, Shirakawa T, Iwatsubo T, Tomita T, et al. Biochemical characterization of the Drosophila wingless signaling pathway based on RNA interference. Mol Cell Biol. 2004;24:2012-24 pubmed
- Chittaranjan S, Xu J, Kuzyk M, Dullat H, Wilton J, Devorkin L, et al. The Drosophila TIPE family member Sigmar interacts with the Ste20-like kinase Misshapen and modulates JNK signaling, cytoskeletal remodeling and autophagy. Biol Open. 2015;4:672-84 pubmed publisher..Together, these findings link Sigmar to the JNK pathway, cytoskeletal remodeling and autophagy activity during salivary gland development, and provide new insights into TIPE family member function. ..
- Murthy M, Schwarz T. The exocyst component Sec5 is required for membrane traffic and polarity in the Drosophila ovary. Development. 2004;131:377-88 pubmed..However, we find the cytoskeleton to be correctly oriented. We conclude that Sec5 is required for directed membrane traffic, and consequently for the establishment of polarity within the developing oocyte. ..
- Choi K, Nam S, Mukhopadhyay B. Par-1 and PP2A: Yin-Yang of Bazooka localization. Fly (Austin). 2007;1:235-7 pubmed..In this extra view, we provide a brief overview and perspective of our findings on the antagonistic function of Par-1 and PP2A in Baz localization during photoreceptor morphogenesis. ..
- Reid D, Muyskens J, Neal J, Gaddini G, Cho L, Wandler A, et al. Identification of genetic modifiers of CagA-induced epithelial disruption in Drosophila. Front Cell Infect Microbiol. 2012;2:24 pubmed publisher..Collectively, these results point to new cellular pathways whose disruption by CagA are likely to contribute to H. pylori-associated disease pathology. ..
- Huang H, Wang S, Yin M, Dong L, Wang C, Wu W, et al. Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association. PLoS Biol. 2013;11:e1001620 pubmed publisher..Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network. ..
- GONCZY P. Mechanisms of spindle positioning: focus on flies and worms. Trends Cell Biol. 2002;12:332-9 pubmed..This article discusses recent findings that indicate how this mechanism might be used for spindle positioning during Drosophila and Caenorhabditis elegans development. ..
- Sung H, Telley I, Papadaki P, Ephrussi A, Surrey T, Rørth P. Drosophila ensconsin promotes productive recruitment of Kinesin-1 to microtubules. Dev Cell. 2008;15:866-76 pubmed publisher..Furthermore, spatial control of motor recruitment can provide additional regulatory control in Par-1 and microtubule-dependent cell polarity. ..
- Leibfried A, Muller S, Ephrussi A. A Cdc42-regulated actin cytoskeleton mediates Drosophila oocyte polarization. Development. 2013;140:362-71 pubmed publisher..This most likely allows for the robustness in symmetry breaking in the cell. ..
- McKim K, Hayashi Hagihara A. mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved. Genes Dev. 1998;12:2932-42 pubmed..In contrast to spo11, mei-W68 is not required for synaptonemal complex formation and does have a mitotic role. ..
- Herzmann S, Krumkamp R, Rode S, Kintrup C, Rumpf S. PAR-1 promotes microtubule breakdown during dendrite pruning in Drosophila. EMBO J. 2017;36:1981-1991 pubmed publisher..Our results shed light on the signaling cascades and epistatic relationships involved in neurite destabilization during dendrite pruning. ..
- Wandler A, Guillemin K. Transgenic expression of the Helicobacter pylori virulence factor CagA promotes apoptosis or tumorigenesis through JNK activation in Drosophila. PLoS Pathog. 2012;8:e1002939 pubmed publisher..These data suggest a potential role for CagA-mediated JNK pathway activation in promoting gastric cancer progression. ..
- McGregor A. How to get ahead: the origin, evolution and function of bicoid. Bioessays. 2005;27:904-13 pubmed..I suggest further comparative studies may allow us to identify the intermediate steps in bcd evolution. This will make bcd a paradigm for the origin and evolution of genes and regulatory networks. ..
- Cox D, Lu B, Sun T, Williams L, Jan Y. Drosophila par-1 is required for oocyte differentiation and microtubule organization. Curr Biol. 2001;11:75-87 pubmed..In both cases, par-1 appears to exert its effects through the regulation of microtubule dynamics and/or stability, and this finding is consistent with the defined role of the mammalian PAR-1 homologs. ..
- Mack N, Georgiou M. The interdependence of the Rho GTPases and apicobasal cell polarity. Small Gtpases. 2014;5:10 pubmed publisher..Regarding this latter theme, we provide further discussion of the potential plasticity of the cell polarity machinery and as a result the possible implications for human disease. ..
- Nam S, Mukhopadhyay B, Choi K. Antagonistic functions of Par-1 kinase and protein phosphatase 2A are required for localization of Bazooka and photoreceptor morphogenesis in Drosophila. Dev Biol. 2007;306:624-35 pubmed..Furthermore, Par-1 gain-of-function phenotypes are strongly enhanced by reduced PP2A function. Thus, we propose that antagonism between PP2A and Par-1 plays a key role in Baz localization at AJ in photoreceptor morphogenesis. ..
- Gailite I, Aerne B, Tapon N. Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system. Proc Natl Acad Sci U S A. 2015;112:E5169-78 pubmed publisher..Thus, we demonstrate a dramatically different wiring of Hpo signaling in neighboring cell populations of distinct developmental origins in the central nervous system. ..
- Ando K, Oka M, Ohtake Y, Hayashishita M, Shimizu S, Hisanaga S, et al. Tau phosphorylation at Alzheimer's disease-related Ser356 contributes to tau stabilization when PAR-1/MARK activity is elevated. Biochem Biophys Res Commun. 2016;478:929-34 pubmed publisher..AD-related phosphorylation of two tau residues, Ser262 and Ser356, by PAR-1/MARK stabilizes tau in the initial phase of mismetabolism, leading to subsequent phosphorylation events, accumulation, ..