Affinage

PARD3

Partitioning defective 3 homolog · UniProt Q8TEW0

Round 2 corrected
Length
1356 aa
Mass
151.4 kDa
Annotated
2026-04-29
130 papers in source corpus 57 papers cited in narrative 57 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PARD3 is a multi-PDZ scaffold protein that nucleates the conserved Par3/Par6/aPKC polarity complex to establish and maintain apical-basal polarity, planar cell polarity, asymmetric cell division, and neuronal polarization across diverse cell types. It self-oligomerizes via its N-terminal CR1 domain into filamentous assemblies required for tight junction formation, directly binds phosphoinositide membranes through its PDZ2 and C-terminal regions, and recruits PTEN, Tiam1/STEF (Rac-GEFs), KIF3A, dynein-LIC2, Exo70 (exocyst), JAM family adhesion molecules, and p75NTR to spatially restrict signaling at cell junctions and cortical domains (PMID:10934474, PMID:12756256, PMID:18082612, PMID:15723052, PMID:28358000, PMID:11447115, PMID:17082460). Its conserved CR3 region acts as a pseudosubstrate inhibitor of aPKC, and phosphorylation by aPKC, PAR-1, ROCK, ERK2, and Ndr1/2 at distinct sites dynamically controls Par3 localization, complex assembly, and downstream Rac, Notch, Hippo/TAZ, and GSK3β signaling (PMID:27554858, PMID:20833361, PMID:23946386, PMID:24928906, PMID:26116754, PMID:19640478). PARD3 mutations in the aPKC-binding region have been identified in cranial neural tube defect cases, where they impair aPKC interaction and tight junction formation (PMID:27925688).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Identification of a conserved Par6–Par3–aPKC–Cdc42 complex linked to tight junctions answered the fundamental question of how polarity determinants are organized at epithelial cell contacts in mammals.

    Evidence Co-immunoprecipitation and pulldown reconstitution of the tripartite Par6/Par3/aPKC complex in mammalian cells

    PMID:10934474 PMID:11257119

    Open questions at the time
    • Stoichiometry of the native complex unknown
    • No structural model of full ternary complex
    • Regulation of complex assembly/disassembly undefined
  2. 2001 High

    Discovery that JAM family adhesion molecules tether Par3 to tight junctions via PDZ domains established the membrane-anchoring mechanism that positions the polarity complex at intercellular contacts.

    Evidence GST pulldown and co-immunoprecipitation mapping JAM–Par3 PDZ1 binding; truncated JAM displaces Par3 from junctions in epithelial and endothelial cells

    PMID:11447115 PMID:12953056

    Open questions at the time
    • Relative contribution of JAM versus lipid-based membrane targeting unresolved
    • Redundancy among JAM family members not fully tested
  3. 2002 High

    Demonstration that Par3 self-oligomerizes via its N-terminal CR1 domain and that this oligomerization is required for tight junction formation revealed a structural prerequisite for polarity complex function.

    Evidence In vitro and in vivo oligomerization assays; CR1 overexpression disrupts aPKC/Par6 distribution and delays TJ assembly in MDCK cells

    PMID:12756256

    Open questions at the time
    • Oligomeric state in vivo not quantified
    • How oligomerization is regulated remained unclear until structural work in 2013
  4. 2004 High

    Identification of KIF3A as the motor that transports Par3 to axon tips resolved how the polarity complex reaches the distal neurite to specify axon identity.

    Evidence Direct Par3–KIF3A binding by co-IP/pulldown; dominant-negative fragments abolish Par3 accumulation at axon tips and prevent neuronal polarization in hippocampal neurons

    PMID:15048131

    Open questions at the time
    • Cargo adaptor mechanism between Par3 and KIF3A not structurally defined
    • Whether other kinesins contribute was unclear
  5. 2005 High

    Two independent studies converged to show that Par3 directly binds and spatially restricts Tiam1/STEF Rac-GEF activity, placing Par3 as a spatial organizer of Rac signaling for both tight junction formation and neuronal polarity.

    Evidence RNAi of Par3 constitutively activates Rac; Rac inhibition or Tiam1 knockdown rescues junction assembly (MDCK); Par3–STEF binding required for Cdc42-induced Rac activation in neuronal cells

    PMID:15723051 PMID:15723052

    Open questions at the time
    • Whether Par3 acts as a scaffold versus allosteric activator of Tiam1 not distinguished
    • Quantitative parameters of Rac activation not measured
  6. 2007 High

    Biochemical and structural demonstration that Par3 PDZ2 directly binds phosphoinositide membranes and PDZ3 recruits PTEN explained how Par3 integrates lipid signaling with cell polarization.

    Evidence NMR and lipid-binding assays for PDZ2; crystal structure of PDZ3–PTEN complex with mutagenesis and MDCK polarization readouts

    PMID:18082612 PMID:18550519

    Open questions at the time
    • How PDZ2 lipid binding cooperates with C-terminal lipid binding (identified in Drosophila) not resolved for mammalian Par3
    • PTEN catalytic contribution at junctions not separated from scaffolding
  7. 2008 High

    Identification of PP1α as the phosphatase that opposes aPKC and PAR-1 phosphorylation of Par3 at multiple sites established that Par3 phosphorylation is dynamically regulated to control 14-3-3 and aPKC binding during junction assembly.

    Evidence Quantitative mass spectrometry for site-specific dephosphorylation; catalytically inactive PP1α delays TJ formation in MDCK cells

    PMID:18641122

    Open questions at the time
    • How PP1α is recruited to Par3 not defined
    • Temporal ordering of phosphorylation/dephosphorylation events during junction biogenesis unknown
  8. 2009 High

    In vivo studies showed that Par3 controls asymmetric division of radial glial progenitors upstream of Notch signaling, extending Par3 function beyond polarity maintenance to cell fate determination in the developing cortex.

    Evidence In utero electroporation of Par3 RNAi/overexpression with Notch epistasis and live imaging in mouse neocortex

    PMID:19640478

    Open questions at the time
    • Direct biochemical link between Par3 and Notch pathway components not established
    • Whether Par3 regulates Numb localization directly or indirectly unclear
  9. 2009 High

    Discovery of Par3–dynein-LIC2 interaction and its role in centrosome positioning revealed that Par3 organizes microtubule dynamics at cell contacts through motor protein recruitment.

    Evidence Co-IP mapping to N-terminal/PDZ1 domains; Par3 knockdown disrupts centrosome centering; TIRF analysis of MT pausing at contacts

    PMID:19540120

    Open questions at the time
    • How Par3-dynein and Par3-KIF3A interactions are coordinated at the same N-terminal region not resolved
    • Whether LIC2 is the sole dynein adaptor for Par3 unknown
  10. 2010 High

    Genetic and biochemical studies in Drosophila demonstrated that aPKC phosphorylation and ROCK phosphorylation of Baz/Par3 control its exclusion from specific membrane domains, establishing phosphorylation as the primary mechanism defining domain boundaries.

    Evidence Phospho-specific antibodies and genetic epistasis with crumbs for aPKC-dependent exclusion; in vitro kinase assays and ROCK loss/gain-of-function for lipid-binding inhibition

    PMID:20434988 PMID:20833361

    Open questions at the time
    • Whether mammalian ROCK performs equivalent phosphorylation not directly shown
    • Relative contributions of aPKC versus ROCK in different polarity contexts not quantified
  11. 2012 High

    Par3 was shown to directly bind, bundle, and stabilize microtubules via its N-terminal domain, with this activity autoinhibited by the C-terminus and relieved by oligomerization, revealing an intrinsic cytoskeletal regulatory activity beyond scaffolding.

    Evidence Reconstituted in vitro MT cosedimentation/bundling assays, TIRF microscopy, and dominant-negative disruption of axon specification in neurons

    PMID:23273878

    Open questions at the time
    • Whether MT bundling activity operates in epithelial cells not tested
    • Structural basis of autoinhibition not resolved at atomic level
  12. 2012 High

    Loss-of-function studies identified Par3 as a tumor and metastasis suppressor in mammary epithelium, acting through restraint of aPKC–JAK/Stat3 and Tiam1/Rac signaling that otherwise promote invasion and E-cadherin junction destabilization.

    Evidence RNAi in mouse mammary gland with oncogenic cooperation assays, tumor transplantation, Rac inhibitor rescue of E-cadherin stability and metastasis

    PMID:23153534 PMID:23263278

    Open questions at the time
    • Whether Par3 loss is a driver or cooperating event in human breast cancer not genetically established
    • Cell-autonomous versus non-cell-autonomous tumor suppression not fully separated
  13. 2013 High

    Crystal and cryo-EM structures of the Par3 NTD revealed a front-to-back filament assembly mode, and structures of PDZ3–VE-cadherin and PDZ3–PTEN complexes defined dual-site binding modes, providing the first atomic framework for Par3 scaffold architecture.

    Evidence X-ray crystallography and cryo-EM of NTD filaments; crystal structures of PDZ3 with VE-cadherin and PTEN peptides; mutagenesis with functional validation

    PMID:18550519 PMID:20047332 PMID:23643951

    Open questions at the time
    • No structure of full-length Par3 or assembled ternary Par complex
    • How NTD filament length is controlled in vivo unknown
  14. 2015 High

    Identification of Par3 as an exocyst receptor via direct Exo70 binding linked polarity to membrane trafficking and cell survival through PIP3/Akt signaling, and discovery of Par3-mediated PP1A–LATS1 interaction connected Par3 to Hippo/TAZ pathway regulation.

    Evidence GST pulldown and domain-specific rescue for Exo70 binding with PI3P/apoptosis readout; co-IP and phosphorylation assays for LATS1/TAZ regulation

    PMID:26116754 PMID:28358000

    Open questions at the time
    • Whether exocyst and Hippo functions of Par3 are spatially segregated not determined
    • Contribution of cytoplasmic versus junctional Par3 pools to Hippo signaling needs further clarification
  15. 2016 High

    The crystal structure of aPKC kinase domain bound to Par3 CR3 revealed a pseudosubstrate inhibition mechanism with dual flanking motifs, resolving how Par3 both binds and inhibits aPKC and how phosphorylation converts CR3 from inhibitor to substrate.

    Evidence X-ray crystallography of aPKC–CR3 complex, in vitro kinase assays with flanking-motif mutants, Drosophila in vivo localization

    PMID:27554858

    Open questions at the time
    • How inhibition is relieved in a physiological context (what triggers the switch) not identified
    • Whether the same mechanism operates for all aPKC isoforms not tested
  16. 2018 High

    Structural studies revealed that Par6 binds Par3 PDZ1 and PDZ3 via a C-terminal PBM, and that aPKC binds Par3 PDZ2 via a separate PBM, defining a multivalent interaction architecture that can simultaneously engage two Par6 molecules and maintain a cortical tether even after aPKC-mediated phosphorylation.

    Evidence X-ray crystallography and NMR of PDZ–PBM complexes; biochemical reconstitution with full-length proteins; Drosophila neuroblast genetics

    PMID:29440511 PMID:32084408

    Open questions at the time
    • Full reconstitution of a native-stoichiometry complex with all partners not achieved
    • In vivo validation in mammalian system for dual Par6 binding not performed
  17. 2019 High

    Conditional knockout in inner ear hair cells established Par3 as essential for planar cell polarity via a Par3–Tiam1/Trio–Rac–Pak signaling axis, extending the Par3–Rac-GEF paradigm from apical-basal to planar polarity.

    Evidence Conditional KO in mouse cochlea; constitutively active Rac1 rescue of PCP defects; co-IP of Par3 with Tiam1 and Trio

    PMID:30814219

    Open questions at the time
    • How Par3 distinguishes apical-basal from planar polarity Rac pools not resolved
    • Role of Trio versus Tiam1 redundancy not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • No full-length structure of Par3 or intact Par3/Par6/aPKC ternary complex exists, and the mechanisms that select between Par3's multiple outputs (tight junctions, Hippo, Rac, Notch, exocyst, MT regulation) in a given cellular context remain undefined.
  • Full-length Par3 structure needed
  • Context-dependent output selection mechanism unknown
  • Relative contributions of oligomeric state, phosphorylation, and partner availability to output switching not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 6 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-1500931 Cell-Cell communication 7 R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-9609507 Protein localization 3 R-HSA-1643685 Disease 2
Partners
DYNC1LI2EXO70JAM3KIF3APARD6APRKCZPTENTIAM1
Complex memberships
Par3/Exo70 exocyst docking complexPar3/Par6/aPKC polarity complexPar3/Tiam1/Rac signaling complex

Evidence

Reading pass · 57 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Par6 forms a tripartite complex with Cdc42-GTP, a human PAR-3 homologue, and the regulatory domains of atypical PKC (aPKC), linking Cdc42 and aPKC to Par3/PAR-3 and implicating this assembly in tight junction formation at epithelial cell-cell contacts. Co-immunoprecipitation, pulldown assays, yeast two-hybrid Nature cell biology High 10934474
2001 aPKC directly interacts with PAR-3 (ASIP) and PAR-6 to form a conserved ternary complex at tight junctions; dominant-negative aPKC mislocalizes PAR-3 and severely disrupts tight junction biogenesis and epithelial apical-basal polarity in MDCK cells. Dominant-negative overexpression, co-immunoprecipitation, immunofluorescence, paracellular permeability assays The Journal of cell biology High 11257119
2001 PAR-3 (ASIP) directly associates with the tight-junction protein junctional adhesion molecule (JAM) in vitro and in vivo via its PDZ domains; overexpression of truncated JAM disrupts PAR-3 localization at intercellular junctions, suggesting JAM tethers the PAR-3/aPKC complex to tight junctions. Co-immunoprecipitation, GST pulldown, immunofluorescence, ectopic expression in fibroblasts/CHO cells The EMBO journal High 11447115
2002 The N-terminal conserved region (CR1) of PAR-3 self-associates to form oligomeric complexes in vivo and in vitro; overexpression of CR1 disrupts aPKC and PAR-6 distribution and delays tight junction formation, demonstrating that PAR-3 self-oligomerization is required for functional tight junctions. Co-immunoprecipitation, biochemical pulldown, overexpression in MDCK cells, transepithelial resistance measurement The Journal of biological chemistry High 12756256
2002 Multiple Par3 splice variants and a related gene Par3L are identified; although all isoforms associate with tight junctions, only a subset of Par3 isoforms bind aPKCs and Par6, demonstrating that aPKC binding is not required for tight junction targeting but influences complex composition. cDNA cloning, co-immunoprecipitation, immunofluorescence in MDCK cells Gene Medium 12234671
2002 ASIP/PAR-3 concentrates at the apical edge of tight junctions and promotes tight junction formation via its aPKC-binding sequence; overexpression of full-length but not aPKC-binding-deficient PAR-3 increases transepithelial resistance and occludin insolubilization, and the aPKC phosphorylation site Ser827 is phosphorylated at the apical tip during early junction formation. Overexpression in MDCK cells, transepithelial resistance, immunogold EM, immunofluorescence Journal of cell science High 12045219
2003 JAM-2 and JAM-3 directly associate with PAR-3 through its first PDZ domain; this association recruits PAR-3 and ZO-1 to cell-cell contacts in endothelial cells, supporting a role for JAM-2/-3 in endothelial cell polarity. GST pulldown, co-immunoprecipitation, ectopic expression in CHO cells, immunofluorescence Journal of cell science High 12953056
2004 PAR-3 directly interacts with KIF3A (a plus-end-directed microtubule motor); aPKC associates with KIF3A through PAR-3. Dominant-negative fragments disrupting PAR-3–KIF3A binding prevent accumulation of PAR-3 and aPKC at axon tips and abolish neuronal polarity, establishing that KIF3A transports PAR-3 to the distal axon to establish neuronal polarity. Co-immunoprecipitation, GST pulldown, dominant-negative expression in cultured hippocampal neurons, immunofluorescence Nature cell biology High 15048131
2004 Zebrafish Pard3 localizes to the apical region of retinal neuroepithelium; antisense morpholino knockdown causes loss of retinal pigmented epithelium, disrupted retinal lamination, and cyclopia, while overexpression also causes cyclopia, demonstrating a critical role in separation of eye fields and retinal lamination. Antisense morpholino knockdown, mRNA overexpression, immunohistochemistry in zebrafish Developmental biology Medium 15081374
2005 Depletion of Par-3 in mammalian epithelial cells profoundly disrupts tight junction assembly; Par-3 directly binds Tiam1 (Rac GEF) via its C-terminal/PDZ3 region, spatially restricting Rac activity. Loss of Par-3 constitutively activates Rac, and dominant-negative Rac or Tiam1 knockdown restores junction assembly, defining a Par-3–Tiam1–Rac pathway for tight junction formation. RNAi knockdown, co-immunoprecipitation, GST pulldown, dominant-negative Rac expression, transepithelial resistance in MDCK cells Nature cell biology High 15723052
2005 PAR-3 directly interacts with Rac-specific GEFs STEF/Tiam1, and STEF forms a complex with PAR-3–aPKC–PAR-6–Cdc42-GTP. Disrupting Cdc42–PAR-6 or PAR-3–STEF binding inhibits Cdc42-induced lamellipodia but not filopodia; PAR-3 is required for Cdc42-induced Rac activation, placing the PAR-6–PAR-3–STEF/Tiam1–Rac axis downstream of Cdc42 in neuronal polarity. Co-immunoprecipitation, GST pulldown, dominant-negative expression, lamellipodia/filopodia assays in N1E-115 cells Nature cell biology High 15723051
2005 Par3 and aPKC adopt polarized localization from the 8-cell mouse embryo stage; dsRNA injection against Par3 or dominant-negative aPKC at the 4-cell stage directs progeny toward the inside (ICM) by increasing differentiative divisions and decreasing outside positioning, demonstrating that Par3/aPKC regulate cell fate allocation in the preimplantation embryo. dsRNA injection, dominant-negative mRNA injection, live imaging, cell fate tracking in mouse embryos Journal of cell science High 15657073
2006 Par-3 directly associates with and recruits the p75 neurotrophin receptor (p75NTR) to the axon-glial junction in Schwann cells; disruption of Par-3 localization by overexpression or knockdown inhibits myelination, establishing that Par-3 localizes asymmetrically and forms a complex with p75NTR necessary for peripheral myelination. Co-immunoprecipitation, GST pulldown, RNAi knockdown, overexpression, immunofluorescence in Schwann cells Science High 17082460
2006 Tyrosine phosphorylation of Par-3 at Y1127 is induced by EGF through Src family kinases (c-Src, c-Yes); phospho-Y1127 reduces Par-3's association with LIMK2, enabling LIMK2 to regulate cofilin phosphorylation dynamics. Y1127F substitution impairs EGF-induced Par-3–LIMK2 dissociation and delays tight junction assembly. Phosphoproteomic profiling, site-directed mutagenesis, co-immunoprecipitation, TJ assembly assays The EMBO journal High 17053785
2006 Lgl is required for disassembly of the apical PAR-3–aPKC–PAR-6 complex domain; siRNA knockdown of Lgl in MDCK cells prevents apical membrane disassembly upon Ca2+ depletion, and this Lgl function is mediated by suppression of the PAR-3–aPKC–PAR-6 complex activity, which is required for lumen formation in 3D collagen gel cultures. siRNA knockdown, Ca2+-switch assay, 3D collagen gel culture, immunofluorescence in MDCK cells Journal of cell science Medium 16638806
2006 A Rich1/Amot complex organizes apical polarity in MDCK cells by binding the PDZ domains of Par-3; Rich1 regulates Cdc42 GTPase activity at tight junctions through this interaction, and Amot's coiled-coil domain is required to localize the complex containing Par-3 to apical membranes. Affinity purification/mass spectrometry, co-immunoprecipitation, RNAi, immunofluorescence Cell High 16678097
2007 The second PDZ domain of Par-3 binds phosphoinositide (PI) lipid membranes with high affinity; the third PDZ domain directly binds PTEN; the PDZ2 membrane-binding capacity is critical for epithelial cell polarization. Thus Par-3 integrates PI signaling through its PDZ domains. Lipid-binding assays, NMR, mutagenesis, epithelial polarization assays in MDCK cells Molecular cell High 18082612
2008 Par-3 PDZ3 binds PTEN via two discrete sites: a canonical PDZ-ligand interaction and a distal charge-charge interaction. This dual-site binding recruits PTEN to junctional membranes of MDCK cells, and this junctional PTEN is specifically required for epithelial cell polarization. X-ray crystallography of PDZ3-PTEN complex, mutagenesis, co-immunoprecipitation, MDCK polarization assay The Journal of biological chemistry High 18550519
2008 Protein phosphatase PP1α binds Par-3 and dephosphorylates Ser-144, Ser-824 and Ser-885, counteracting aPKC and PAR-1 phosphorylation; this regulates 14-3-3 and aPKCζ binding to Par-3. Catalytically inactive PP1α expression severely delays tight junction formation, establishing PP1α as the phosphatase that dynamically controls Par-3 phosphorylation. Co-immunoprecipitation, multiple reaction monitoring mass spectrometry, catalytic-dead mutant expression, TJ formation assay in MDCKII Proceedings of the National Academy of Sciences of the United States of America High 18641122
2009 mPar3 exhibits dynamic and asymmetric distribution in radial glial progenitors; removal or ectopic expression of mPar3 prevents asymmetric division. mPar3 expression level affects Notch signaling, and manipulations of Notch signaling or Numb expression suppress mPar3 regulation of radial glial cell division and daughter cell fate, placing mPar3 upstream of Notch in cortical progenitor asymmetric division. RNAi knockdown, overexpression, in utero electroporation, live imaging, genetic epistasis in mouse neocortex Neuron High 19640478
2009 Par3 associates with dynein through its N-terminal dimerization and PDZ1 domains, specifically via dynein light intermediate chain 2 (LIC2). Par3 knockdown or overexpression of the Par3 N-terminal domain disrupts centrosome positioning at the cell center; Par3 at cell-cell contacts promotes local MT pausing via LIC2, thereby contributing to centrosome orientation during migration. Co-immunoprecipitation, siRNA knockdown, live imaging, MT dynamics analysis by TIRF Current biology : CB High 19540120
2009 The Par3/aPKC interaction is essential for mammary gland morphogenesis; Par3 depletion via shRNA disrupts ductal development with hyperplasia and luminal filling; the aPKC-binding domain of Par3 restricts Par3 and aPKC to the apical region in vivo, and direct Par3–aPKC binding is required for normal mammary morphogenesis and progenitor differentiation. shRNA lentiviral KD, mammary gland transplantation, immunofluorescence in mouse mammary gland Genes & development High 19528321
2010 aPKC phosphorylates Bazooka/PAR-3 to exclude it from the apical domain in Drosophila epithelia; removal of Baz from the PAR-6/aPKC complex also requires the Crumbs complex (which blocks Baz–PAR-6 interaction). Mislocalized Baz recruits adherens junction components apically, expanding lateral and eliminating apical domain, thereby defining the apical/lateral border. Genetic analysis, phospho-specific antibodies, epistasis with crumbs mutants, confocal imaging in Drosophila epithelia Cell High 20434988
2010 Membrane targeting of Drosophila Bazooka/PAR-3 is mediated by a conserved C-terminal region that directly binds phosphoinositide lipids; PDZ domains are dispensable for cortical localization. This direct PI-membrane interaction is required for correct Baz localization in epithelia, neuroblasts, follicle cells and the oocyte. Structure-function analysis with GFP-tagged transgenes, lipid-binding assays, Drosophila genetics in four cell types Current biology : CB High 20303268
2010 Beta1 integrin functions upstream of Par3 in endothelial cells; loss of beta1 integrin decreases Par3 expression and causes mislocalization of polarity markers and defective arterial lumen formation. Replacement of Par3 protein in beta1-deficient vessels partially rescues luminal occlusion, placing Par3 downstream of beta1 integrin in a pathway for endothelial cell polarity and lumen formation. Conditional knockout mouse, rescue experiment with Par3 protein, immunofluorescence, histology Developmental cell High 20152176
2010 Rho-kinase (ROCK) phosphorylates the C-terminal domain of Baz/PAR-3, inhibiting its interaction with phosphoinositide membrane lipids; ROCK is asymmetrically enriched at anterior/posterior borders complementary to Baz, and loss of ROCK expands the Baz domain. Activated ROCK is sufficient to exclude Baz from the cortex, demonstrating that ROCK controls planar polarity by targeting Baz distribution. Genetic loss- and gain-of-function, phosphorylation assays, in vitro kinase assay, Drosophila embryo imaging Developmental cell High 20833361
2010 Baz/PAR-3 recruits Stardust to the plasma membrane by direct interaction between the PDZ domain of Stardust and a region of Baz containing an aPKC phosphorylation site; aPKC phosphorylation of Baz causes dissociation of the Baz-Stardust complex. Overexpression of nonphosphorylatable Baz blocks Sdt dissociation and causes polarity phenotypes similar to crumbs/sdt mutations. Co-immunoprecipitation, phospho-mutant overexpression, Drosophila genetics, superresolution microscopy The Journal of cell biology High 20819933
2010 Pard3A undergoes proteasomal degradation by the Siah E3 ubiquitin ligase; gain of Pard3A function and Siah loss of function induce precocious radial migration of cerebellar granule neurons. Pard3A promotes adhesive interactions for germinal zone exit by recruiting epithelial tight junction adhesion molecule C (JAM-C) to the neuronal cell surface. Gain/loss-of-function, time-lapse imaging, cell contact probe assay, proteasome inhibitor experiments in cerebellum Science High 21109632
2010 PAR-3 is required for MTOC/centrosome positioning during zebrafish neurulation; Pard3 depletion results in failure to transition microtubule network from radial to linear organization, disrupted centrosome positioning, and hydrocephalus. Microtubules function with Pard3 cooperatively to position the centrosome during mesenchyme-to-epithelium transition. Morpholino knockdown, immunofluorescence, live imaging in zebrafish neural progenitors Developmental biology Medium 20138861
2011 Willin and Par3 cooperatively recruit aPKC and Par6 to apical junctional complexes; simultaneous depletion of Willin and Par3 removes aPKC/Par6 from AJCs and induces apical constriction through upregulation of ROCK at junctions. aPKC phosphorylates ROCK and suppresses its junctional localization, revealing a Willin/Par3–aPKC–ROCK pathway controlling epithelial apical morphology. siRNA double-knockdown, co-immunoprecipitation, in vitro kinase assay, immunofluorescence in MDCK cells Nature cell biology High 21685893
2012 Loss of Par3 in mammary epithelial cells induces MMP9, destroys extracellular matrix, and promotes invasion via aPKC-dependent JAK/Stat3 activation; Par3 depletion in combination with Notch or Ras reduced tumor latency and produced invasive/metastatic tumors in mice, identifying Par3 as a suppressor of signaling pathways relevant to invasive breast cancer. RNAi in mouse mammary gland, oncogenic cooperation assay, tumor transplantation, pathway inhibitor experiments Cancer cell High 23153534
2012 Loss of Par3 inhibits E-cadherin junction stability and decreases cell-cell cohesion in a Tiam1/Rac-GTP-dependent manner; inhibition of Tiam1/Rac restores E-cadherin junction stability and blocks invasion cooperating with ErbB2, indicating that Par3 suppresses metastatic behavior by maintaining cell-cell cohesion through Tiam1/Rac regulation. RNAi, co-immunoprecipitation, junction stability assays, in vivo metastasis models, Rac inhibitor experiments Nature cell biology High 23263278
2012 The N-terminal portion of mPar3 directly binds, bundles, and stabilizes microtubules; this activity is suppressed by intramolecular interaction with its C-terminal portion and is relieved by intermolecular oligomerization. Disruption of this microtubule-regulatory activity impairs axon specification, demonstrating a direct role for mPar3 in microtubule organization for neuronal polarization. In vitro microtubule co-sedimentation, bundling assays, TIRF microscopy, dominant-negative in neurons Developmental cell High 23273878
2012 Par3 loss of function promotes apoptosis in mammary epithelial cells; oncogenic Notch overcomes this apoptosis to reveal a pro-proliferative Rac1/JNK-dependent pathway. Loss of Par3 deregulates Rac1 activity to activate JNK-dependent proliferation and tumor growth. RNAi, dominant-negative Rac1, JNK inhibitor, apoptosis and proliferation assays in mammary organoids Oncogene Medium 25109337
2013 BAI1 (brain-specific angiogenesis inhibitor 1) interacts with Par3/Tiam1 and recruits these proteins to synaptic sites; BAI1 knockdown mislocalizes Par3/Tiam1, reduces activated Rac1 and F-actin from spines. A BAI1 mutant unable to bind Par3/Tiam1 fails to rescue spine and synapse defects, identifying BAI1 as a cell surface receptor that targets the Par3/Tiam1 complex to synapses. Co-immunoprecipitation, RNAi, domain-specific rescue, immunofluorescence in neurons The Journal of neuroscience High 23595754
2013 ERK2 directly interacts with Par3 and phosphorylates it at Ser-1116; phospho-S1116 Par3 accumulates at axonal tips in an ERK2-dependent manner but shows reduced binding to KIF3A (not to Par6 or aPKC). A phosphomimetic Par3-S1116D mutant shows slower axonal transport and fails to rescue neuronal polarity, establishing an ERK2–Par3–KIF3A regulatory axis for neuronal polarity. Co-immunoprecipitation, in vitro kinase assay, phosphomimetic mutant rescue, live axonal transport imaging in hippocampal neurons The Journal of neuroscience High 23946386
2013 Par3 PDZ3 binds the C-terminal tail of VE-cadherin using both canonical and distal charge-charge interaction modes (involving Asp777 of VE-Cad and Arg609 of Par3-PDZ3); phosphorylation of VE-Cad at Ser776 increases its affinity for Par3, demonstrating phosphorylation-dependent modulation of PDZ-ligand interactions outside the canonical binding site. NMR spectroscopy, X-ray crystallography, fluorescence polarization, mutagenesis Biochemistry High 20047332
2013 Crystal structure of Par-3 N-terminal domain (NTD) and cryo-EM filament structure reveal a 'front-to-back' self-association mode mediated by electrostatic interactions at both lateral and longitudinal interfaces; disruption of either interface impairs Par-3 NTD self-association and Par-3-mediated epithelial polarization. X-ray crystallography, cryo-electron microscopy, mutagenesis, epithelial polarization assay Structure High 23643951
2013 Polycystin-1 (PC-1) associates with Par3, favouring assembly of a Par3/aPKC complex; PC-1 regulates cell polarity for oriented cell migration and a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney causes defective convergent extension and renal cyst formation, placing Par3 downstream of PC-1 in tubular morphogenesis. Co-immunoprecipitation, conditional KO in mouse kidney, 3D morphogenesis assays Nature communications High 24153433
2013 Atp6ap2/(pro)renin receptor directly interacts with PAR3 as demonstrated by co-immunoprecipitation from retinal homogenates and yeast two-hybrid assay; this interaction is required for laminar formation during retinal development, with Atp6ap2 CKO mice showing Par3 mislocalization and retinal disorganization. Co-immunoprecipitation, yeast two-hybrid, conditional KO in mouse retina The Journal of neuroscience Medium 24305829
2014 Par3-mInsc and Gαi3 act cooperatively and independently to polarize LGN and promote perpendicular epidermal cell divisions; loss of either gene randomizes division angles, while combined loss of Gnai3 and mInsc causes mostly planar divisions resembling LGN loss, establishing Par3-mInsc as upstream of LGN in the spindle orientation hierarchy. Conditional KO mice, lentiviral in vivo RNAi, genetic epistasis, division angle quantification Nature cell biology High 25016959
2014 Par3L (Par3-like) binds and inhibits the kinase activity of tumor suppressor Lkb1; Par3L is essential for mammary stem cell maintenance, and ablation causes rapid stem cell loss. This Par3L–Lkb1 interaction is the key functional mechanism, as Par3 does not interact with Lkb1 or rescue Par3L loss. Co-immunoprecipitation, in vitro kinase assay, conditional KO in mouse mammary gland, lineage tracing Nature cell biology High 24859006
2014 Ndr1/Ndr2 kinases phosphorylate Par3 at Ser383 downstream of Rassf5; this phosphorylation inhibits Par3's interaction with dynein, polarizing Par3 distribution and reinforcing axon specification. Loss of Rassf5 or Ndr1/2 causes supernumerary axons in hippocampal neurons, defining a Rassf5–Ndr–Par3 signaling cascade. In vitro kinase assay, co-immunoprecipitation, RNAi, phospho-mutant rescue in hippocampal neurons Journal of cell science High 24928906
2015 PARD3 promotes PP1A–LATS1 interaction, inducing LATS1 dephosphorylation and inactivation, which leads to TAZ dephosphorylation and activation; cytoplasmic (not tight-junction-associated) PARD3 is responsible for this Hippo pathway regulation, providing a mechanism for PARD3 growth-promoting activity. Co-immunoprecipitation, phosphorylation assays, knockdown/overexpression, TAZ reporter assays EMBO reports High 26116754
2015 Par3 is essential for mammary cell survival by serving as an exocyst receptor: a small region of PAR3 directly binds Exo70 and is sufficient for exocyst docking and basolateral membrane-protein delivery. Loss of this domain causes apoptosis through PI3-trisphosphate depletion and decreased Akt phosphorylation, establishing Par3 as the exocyst receptor at tight junctions. Co-immunoprecipitation, GST pulldown, domain-specific rescue, PI3P measurements, apoptosis assays in mammary epithelial cells Nature communications High 28358000
2015 Shp2 interacts with PAR3 via its SH2 domain and attenuates PAR3 phosphorylation and formation of the PAR3/PAR6/aPKC complex; ectopic Shp2 disrupts cell polarity and promotes EMT in prostate cancer cells, while Shp2 knockdown has the opposite effect. Co-immunoprecipitation, overexpression/knockdown, polarity and EMT marker assays in prostate cancer cells Oncogene Medium 26050620
2015 Par3 controls B-cell receptor-antigen microcluster gathering and MTOC polarization at the immune synapse by facilitating local dynein recruitment; Par3 is required for antigen presentation to T-lymphocytes, coupling early BCR signaling to late lysosome exocytosis. Knockdown, immunofluorescence, live imaging, antigen presentation assays in B-cells Molecular biology of the cell Medium 25631815
2015 Huntingtin (HTT) forms a complex with PAR3, aPKC, and RAB11A and ensures microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A; HTT depletion alters apical PAR3-aPKC localization, ductal morphogenesis, and lumen formation in mouse mammary epithelium. Co-immunoprecipitation, conditional KO in mouse mammary gland, live vesicle trafficking imaging, immunofluorescence PLoS biology High 25942483
2015 PARD3 mutations in the aPKC-binding region identified in cranial neural tube defect (NTD) cases impair aPKC binding or interaction, resulting in defective tight junction formation; PARD3 knockdown in neural progenitor cells and chick embryos causes abnormal cell polarity and compromised neuroepithelial polarization. Patient variant functional analysis, co-immunoprecipitation, TJ formation in MDCK/HEK293T, morpholino knockdown in chick Human mutation Medium 27925688
2016 Par3 conserved region 3 (CR3) forms a tight inhibitory complex with primed aPKC kinase domain, blocking substrate access via two flanking motifs: one disrupts aPKC N-lobe contacts and the other provides high-affinity anchoring. Mutation of either motif switches CR3 from inhibitor to efficient substrate, relocates Par3/Baz from apical domain to adherens junctions in vivo. X-ray crystallography of aPKC-CR3 complex, mutagenesis, in vitro kinase assay, Drosophila in vivo localization Developmental cell High 27554858
2017 Epidermal keratinocyte-specific Par3 inactivation up-regulates surface P-cadherin, which promotes melanocyte proliferation and phenotypic switch toward dedifferentiation in a non-cell-autonomous manner; low epidermal PAR3 and high P-cadherin correlate with human melanoma progression. Conditional KO in mouse epidermis, autochthonous melanoma model, P-cadherin blocking, immunofluorescence The Journal of experimental medicine Medium 28096290
2017 HPV-18 E6 oncoprotein binds Par3 in a PDZ-dependent manner and induces mislocalization of Par3 without significant reduction in protein levels; this binding delays tight junction formation in calcium switch assays, providing a mechanism for HPV-induced loss of cell polarity. Co-immunoprecipitation, PDZ-binding mutant analysis, calcium switch TJ formation assay, immunofluorescence Molecular oncology Medium 24462519
2018 Par3 PDZ1 and PDZ3 (but not PDZ2) engage in canonical interaction with a PDZ-binding motif (PBM) in Par6's C-terminus, as revealed by X-ray crystallography and NMR; this PBM is essential for Par6-Par3 interaction in vitro and for Par3-mediated membrane localization of Par6. Par3 can potentially recruit two Par6 proteins simultaneously via PDZ1 and PDZ3. X-ray crystallography, NMR spectroscopy, mutagenesis, co-immunoprecipitation, cell localization assay Science signaling High 29440511
2018 PAR-3 controls endothelial planar cell polarity under laminar flow by acting as a gatekeeper of GSK3β activity; flow-induced spatial distribution of PAR-3/aPKCλ and aPKCλ/GSK3β complexes controls local GSK3β activity and regulates flow-dependent polarity axis, while this spatial information is not required for flow-induced anti-inflammatory responses. Conditional KO in endothelial cells, co-immunoprecipitation, flow chamber experiments, immunofluorescence EMBO reports Medium 30018153
2019 Par3 is essential for planar cell polarity of inner ear hair cells; Par3 deletion disrupts hair bundle orientation, kinocilium positioning, and basal body planar polarity. Par3 interacts with and regulates the localization of Rac-GEFs Tiam1 and Trio, stimulating Rac-Pak signaling; constitutively active Rac1 rescues PCP defects in Par3-deficient cochleae, establishing a Par3–GEF–Rac axis for PCP. Conditional KO in mouse inner ear, co-immunoprecipitation, constitutively active Rac rescue, immunofluorescence, genetic mosaic analysis Proceedings of the National Academy of Sciences of the United States of America High 30814219
2020 A conserved PDZ-binding motif (PBM) in aPKC interacts with the second PDZ domain of Par-3; this interaction is required for cortical targeting of the Par complex in asymmetrically dividing Drosophila neuroblasts. aPKC-mediated phosphorylation of Par-3 dissociates the phosphorylation site from aPKC's kinase domain but does not disrupt the Par-3 PDZ2–aPKC PBM interaction, maintaining a persistent cortical tether. Biochemical reconstitution with purified full-length proteins, phosphorylation assays, Drosophila neuroblast genetics Current biology : CB High 32084408
2023 In muscle satellite cells, the polarity protein Pard3 induces TAZ expression through p38 MAPK signaling; Pard3 promotes asymmetric satellite cell division with higher TAZ in committed cells, and this Pard3–p38 MAPK–TAZ axis is required for satellite cell activation during exercise-induced muscle regeneration. Satellite cell-specific TAZ KO mice, exercise training, co-localization, p38 MAPK inhibitor, immunofluorescence and immunoblot Journal of cachexia, sarcopenia and muscle Medium 37923703

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature cell biology 760 10934474
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Molecular & cellular proteomics : MCP 434 15951569
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2009 Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nature genetics 388 19684603
2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Current biology : CB 386 15324660
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2005 Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nature cell biology 382 15723052
2001 Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. The Journal of cell biology 378 11257119
1996 Generation and analysis of 280,000 human expressed sequence tags. Genome research 376 8889549
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1996 armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila. The Journal of cell biology 330 8698811
1999 Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts. Nature 314 10591217
2005 PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nature cell biology 313 15723051
2001 The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). The EMBO journal 310 11447115
2006 A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 302 16678097
2003 Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nature cell biology 301 12510193
2007 Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3. Developmental cell 292 17609107
2010 Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nature cell biology 285 21170030
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2009 Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex. Neuron 274 19640478
2004 Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity. Nature cell biology 232 15048131
2010 aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells. Cell 226 20434988
2010 Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Developmental cell 220 20152176
2005 Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo. Journal of cell science 216 15657073
2010 Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation. Developmental cell 212 20833361
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2003 The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity. Journal of cell science 203 12953056
2012 Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. Cancer cell 185 23153534
2007 PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Molecular cell 154 18082612
2009 Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration. Current biology : CB 152 19540120
2002 Protection against thrombosis in mice lacking PAR3. Blood 150 12384423
2002 Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. Journal of cell science 141 12045219
2012 Loss of Par3 promotes breast cancer metastasis by compromising cell-cell cohesion. Nature cell biology 131 23263278
2007 Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitis. Gut 129 17989107
2006 The polarity protein Par-3 directly interacts with p75NTR to regulate myelination. Science (New York, N.Y.) 124 17082460
2007 Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC. Journal of cell science 122 17726059
2013 The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites. The Journal of neuroscience : the official journal of the Society for Neuroscience 118 23595754
2013 The Par3/Par6/aPKC complex and epithelial cell polarity. Experimental cell research 115 23535009
2009 The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis. Genes & development 114 19528321
2003 Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions. The Journal of biological chemistry 111 12756256
2008 Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and blood-testis barrier restructuring during spermatogenesis. Proceedings of the National Academy of Sciences of the United States of America 109 18621709
2004 Requirement for Par-6 and Bazooka in Drosophila border cell migration. Development (Cambridge, England) 108 15456726
2014 Par3-mInsc and Gαi3 cooperate to promote oriented epidermal cell divisions through LGN. Nature cell biology 107 25016959
2010 Membrane targeting of Bazooka/PAR-3 is mediated by direct binding to phosphoinositide lipids. Current biology : CB 106 20303268
2012 A role for the centrosome and PAR-3 in the hand-off of MTOC function during epithelial polarization. Current biology : CB 103 22425160
2006 Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity. Journal of cell science 101 16638806
2011 Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation. Nature cell biology 100 21685893
2008 Par-3-mediated junctional localization of the lipid phosphatase PTEN is required for cell polarity establishment. The Journal of biological chemistry 100 18550519
2012 Tumor type-dependent function of the par3 polarity protein in skin tumorigenesis. Cancer cell 99 22975380
2009 Independent cadherin-catenin and Bazooka clusters interact to assemble adherens junctions. The Journal of cell biology 97 19468069
2006 Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation. The Journal of investigative dermatology 91 17110935
2010 Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity in epithelia. The Journal of cell biology 77 20819933
2010 Siah regulation of Pard3A controls neuronal cell adhesion during germinal zone exit. Science (New York, N.Y.) 77 21109632
2008 Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3. Proceedings of the National Academy of Sciences of the United States of America 75 18641122
2001 Bazooka and PAR-6 are required with PAR-1 for the maintenance of oocyte fate in Drosophila. Current biology : CB 75 11516655
2003 Distinct roles of Bazooka and Stardust in the specification of Drosophila photoreceptor membrane architecture. Proceedings of the National Academy of Sciences of the United States of America 71 14569003
2012 Regulation of microtubule stability and organization by mammalian Par3 in specifying neuronal polarity. Developmental cell 69 23273878
2007 Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4. Proceedings of the National Academy of Sciences of the United States of America 66 17606903
2006 Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling. The EMBO journal 64 17053785
2002 Multiple splice variants of Par3 and of a novel related gene, Par3L, produce proteins with different binding properties. Gene 63 12234671
2009 PP2A antagonizes phosphorylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts. Developmental cell 62 19531360
2017 Listeriolysin O: from bazooka to Swiss army knife. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 61 28630160
1995 An arabinose-inducible expression vector, pAR3, compatible with ColE1-derived plasmids. Gene 61 7789799
2015 Shp2 promotes metastasis of prostate cancer by attenuating the PAR3/PAR6/aPKC polarity protein complex and enhancing epithelial-to-mesenchymal transition. Oncogene 58 26050620
2017 The Par3 polarity protein is an exocyst receptor essential for mammary cell survival. Nature communications 56 28358000
2013 An activated protein C analog stimulates neuronal production by human neural progenitor cells via a PAR1-PAR3-S1PR1-Akt pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 23554499
2004 The zebrafish Pard3 ortholog is required for separation of the eye fields and retinal lamination. Developmental biology 55 15081374
2016 aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization. Developmental cell 54 27554858
2014 PI(4,5)P2 produced by the PI4P5K SKTL controls apical size by tethering PAR-3 in Drosophila epithelial cells. Current biology : CB 54 24768049
2013 Dynamic microtubules produce an asymmetric E-cadherin-Bazooka complex to maintain segment boundaries. The Journal of cell biology 54 23751496
2002 PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions. Biochemical and biophysical research communications 53 12459187
2015 PARD3 induces TAZ activation and cell growth by promoting LATS1 and PP1 interaction. EMBO reports 50 26116754
2012 Regulation of myosin activation during cell-cell contact formation by Par3-Lgl antagonism: entosis without matrix detachment. Molecular biology of the cell 49 22496418
2013 Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis. Nature communications 46 24153433
2010 TGF-{beta}-induced MiR-491-5p expression promotes Par-3 degradation in rat proximal tubular epithelial cells. The Journal of biological chemistry 46 20966078
2018 MicroRNA 483-3p targets Pard3 to potentiate TGF-β1-induced cell migration, invasion, and epithelial-mesenchymal transition in anaplastic thyroid cancer cells. Oncogene 45 30171257
2010 The polarity protein Pard3 is required for centrosome positioning during neurulation. Developmental biology 45 20138861
2019 Par3 is essential for the establishment of planar cell polarity of inner ear hair cells. Proceedings of the National Academy of Sciences of the United States of America 44 30814219
2019 LncRNA SLCO4A1-AS1 promotes colorectal cancer cell proliferation by enhancing autophagy via miR-508-3p/PARD3 axis. Aging 44 31308265
2015 PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion. Cancer research 43 25833829
2014 Noncanonical PAR3 activation by factor Xa identifies a novel pathway for Tie2 activation and stabilization of vascular integrity. Blood 43 25320242
2010 Distal interactions within the par3-VE-cadherin complex. Biochemistry 43 20047332
2004 PAR-3 is required for epithelial cell polarity in the distal spermatheca of C. elegans. Development (Cambridge, England) 43 15151982
2014 The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance. Nature cell biology 42 24859006
2012 Assembly of Bazooka polarity landmarks through a multifaceted membrane-association mechanism. Journal of cell science 42 22303000
2000 Meiotic maturation induces animal-vegetal asymmetric distribution of aPKC and ASIP/PAR-3 in Xenopus oocytes. Development (Cambridge, England) 41 11060229
2010 Different domains of C. elegans PAR-3 are required at different times in development. Developmental biology 39 20678977
2017 The epidermal polarity protein Par3 is a non-cell autonomous suppressor of malignant melanoma. The Journal of experimental medicine 38 28096290
2017 Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells. Nature communications 38 28827518
2001 Bazooka is required for localization of determinants and controlling proliferation in the sensory organ precursor cell lineage in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 38 11734647
2015 Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC. PLoS biology 37 25942483
2014 Human papillomavirus (HPV)-18 E6 oncoprotein interferes with the epithelial cell polarity Par3 protein. Molecular oncology 36 24462519
2014 Oncogenic suppression of apoptosis uncovers a Rac1/JNK proliferation pathway activated by loss of Par3. Oncogene 36 25109337
2009 A critical step for postsynaptic F-actin organization: regulation of Baz/Par-3 localization by aPKC and PTEN. Developmental neurobiology 36 19472188
2015 Polarity protein Par3 controls B-cell receptor dynamics and antigen extraction at the immune synapse. Molecular biology of the cell 35 25631815
2018 PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow. EMBO reports 34 30018153
2018 PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization. Cellular and molecular life sciences : CMLS 33 29696344
2017 Downregulation of PKCζ/Pard3/Pard6b is responsible for lung adenocarcinoma cell EMT and invasion. Cellular signalling 33 28652146
2018 Structural basis for the interaction between the cell polarity proteins Par3 and Par6. Science signaling 30 29440511
2013 ERK2-mediated phosphorylation of Par3 regulates neuronal polarization. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 23946386
2013 Atp6ap2/(pro)renin receptor interacts with Par3 as a cell polarity determinant required for laminar formation during retinal development in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 24305829
2017 Rare Deleterious PARD3 Variants in the aPKC-Binding Region are Implicated in the Pathogenesis of Human Cranial Neural Tube Defects Via Disrupting Apical Tight Junction Formation. Human mutation 29 27925688
2008 Differential expression of the tight junction proteins, claudin-1, claudin-4, occludin, ZO-1, and PAR3, in the ameloblasts of rat upper incisors. Anatomical record (Hoboken, N.J. : 2007) 29 18384062
2017 Polarity protein Par3/Bazooka follows myosin-dependent junction repositioning. Developmental biology 28 28063874
2014 Pard3 regulates contact between neural crest cells and the timing of Schwann cell differentiation but is not essential for neural crest migration or myelination. Developmental dynamics : an official publication of the American Association of Anatomists 28 25130183
2006 Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3. Biochemical and biophysical research communications 28 16458856
2015 Bazooka/PAR3 is dispensable for polarity in Drosophila follicular epithelial cells. Biology open 27 25770183
2020 A Conserved PDZ-Binding Motif in aPKC Interacts with Par-3 and Mediates Cortical Polarity. Current biology : CB 26 32084408
2016 KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation. PLoS pathogens 26 27463802
2013 Structural insights into the intrinsic self-assembly of Par-3 N-terminal domain. Structure (London, England : 1993) 26 23643951
2011 Altered nephrin and podoplanin distribution is associated with disturbed polarity protein PARD-3 and PARD-6 expressions in podocytes from preeclampsia. Reproductive sciences (Thousand Oaks, Calif.) 26 21422051
2005 Proteinase-activated receptors (PARs)--the PAR3 Neo-N-terminal peptide TFRGAP interacts with PAR1. Regulatory peptides 26 15582715
2023 TAZ stimulates exercise-induced muscle satellite cell activation via Pard3-p38 MAPK-TAZ signalling axis. Journal of cachexia, sarcopenia and muscle 25 37923703
2014 Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway. Journal of cell science 25 24928906
2021 Par-3 family proteins in cell polarity & adhesion. The FEBS journal 24 33565714
2018 Shared and independent functions of aPKCλ and Par3 in skin tumorigenesis. Oncogene 24 29789715