| 2000 |
PARD6B (Par6) was identified as a key adaptor protein that forms a complex with Cdc42-GTP, a human homologue of PAR-3, and the regulatory domains of atypical protein kinase C (aPKC), linking Cdc42 to aPKC and implicated in the formation of normal tight junctions at epithelial cell-cell contacts. |
Co-immunoprecipitation, yeast two-hybrid, and dominant-negative functional assays in MDCK cells |
Nature cell biology |
High |
10934474
|
| 2001 |
Human PAR6 homologues (PAR6alpha/PARD6A, PAR6beta/PARD6B, PAR6gamma/PARD6G) were cloned; PARD6B harbors a PDZ domain and a CRIB-like motif and directly interacts with GTP-bound Rac and Cdc42 via the CRIB-like motif, and with aPKC isoforms (PKCiota/lambda and PKCzeta) via its N-terminal region, forming a ternary complex both in vitro and in vivo. |
cDNA cloning, GST pulldown, co-immunoprecipitation, co-localization in HeLa/COS-7 cells |
Genes to cells : devoted to molecular & cellular mechanisms |
High |
11260256
|
| 2001 |
PARD6B is part of the evolutionarily conserved aPKC-PAR-6-PAR-3 ternary complex that localizes to the apical junctional region of MDCK cells; dominant-negative aPKC causes mislocalization of PAR-3 and severe disruption of tight junction biogenesis and epithelial cell surface polarity. |
Dominant-negative overexpression, immunocytochemistry, paracellular diffusion assays in MDCK cells |
The Journal of cell biology |
High |
11257119
|
| 2003 |
Comprehensive tandem affinity purification-mass spectrometry of human Par proteins revealed that PARD6B (Par-6b) participates in a highly interconnected polarity network, forming core complexes with Par-3 and aPKC as well as with more than 50 novel interactors, establishing the Par-3/Par-6/aPKC module as a central hub of the polarity network. |
Tandem affinity purification (TAP) coupled to tandem mass spectrometry from cultured cells |
The Journal of biological chemistry |
High |
14676191
|
| 2003 |
PARD6B directly interacts with PALS1 (a Crumbs complex component) through its PDZ domain in a manner regulated by Cdc42-GTP, biochemically linking the Par6-aPKC-Par3 polarity complex to the Crumbs-PALS1-PATJ complex; disruption of PALS1 mislocalizes PARD6B and ZO-1 in MDCK cells. |
Co-immunoprecipitation, GST pulldown, dominant-negative overexpression in MDCK cells |
Nature cell biology |
High |
12545177
|
| 2003 |
Mammalian Lgl (mLgl) competes with PAR-3 for binding to the PAR-6/aPKC complex; mLgl forms an independent complex with PAR-6 (including PARD6B) and aPKC, is phosphorylated by aPKC, and is segregated to the basolateral membrane after polarization. Overexpression of the mLgl/PAR-6/aPKC complex suppresses epithelial junction formation. |
Co-immunoprecipitation, overexpression studies, immunofluorescence in MDCK cells |
Current biology : CB |
High |
12725730
|
| 2003 |
Crystal structure of PB1 domain heterodimers revealed that aPKC (PKCzeta) binds both Par6 and p62 via conserved front-to-back electrostatic interactions between the OPCA motif and basic residues; this structural mechanism governs PARD6B-aPKC complex assembly. |
X-ray crystallography plus mutagenesis of PB1 domain interactions |
Molecular cell |
High |
12887891
|
| 2005 |
PARD6B is asymmetrically localized to the apical pole of mouse blastomeres beginning at the 8-cell stage during compaction, independently of cell-cell contact, and colocalizes with aPKCzeta at the apical domain; at the 16-cell stage, PARD6B/PARD3/aPKCzeta colocalize at tight junctions in blastocysts. |
Immunofluorescence confocal imaging in preimplantation mouse embryos |
Developmental biology |
Medium |
15950600
|
| 2005 |
SRC-3/AIB1 coactivator, together with estrogen receptor-alpha, directly regulates PARD6B gene expression in MCF-7 breast cancer cells, as demonstrated by ChIP and SRC-family siRNA knockdown. |
Chromatin immunoprecipitation (ChIP), genomic mapping, siRNA knockdown of SRC-1/2/3 |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
15677324
|
| 2009 |
Formation of the PAR-3-aPKC-PARD6B complex is essential for apical membrane protein delivery and apical domain development in MDCK cells; a PAR-3 point mutant (S827/829A) that cannot interact with aPKC fails to rescue apical domain defects caused by PAR-3 knockdown, while tight junction maturation does not require this interaction. |
siRNA knockdown, rescue with point-mutant PAR-3, 2D and 3D MDCK culture, confocal imaging |
Journal of cell science |
High |
19401335
|
| 2010 |
PARD6B is essential for trophectoderm formation in the preimplantation mouse embryo; Pard6b knockdown (RNAi into zygotes) caused failure of blastocyst cavity formation, abnormal actin and ZO-1 distribution, absence of apical aPKCzeta localization, reduced CDX2 expression in outer cells, and chimera experiments showed the defect is cell-autonomous. |
RNAi microinjection into zygotes, immunofluorescence, chimera analysis |
Biology of reproduction |
High |
20505164
|
| 2011 |
PARD6B and aPKC are required for correct mitotic spindle orientation during Caco-2 epithelial morphogenesis in 3D Matrigel; depletion of Par6B causes misorientation of the mitotic spindle, mispositioning of the nascent apical surface, and multi-lumen cyst formation. Mechanistically, PARD6B recruits aPKC to the apical surface, while aPKC (in a kinase-independent manner) protects PARD6B from proteasomal degradation. |
siRNA depletion, dominant-negative expression, 3D Matrigel cyst assay, immunofluorescence, proteasome inhibitor rescue |
The Journal of biological chemistry |
High |
21300793
|
| 2012 |
PAR6B is required for tight junction assembly and apical membrane localization of activated aPKCzeta in breast cancer MCF7 cells; siRNA-mediated PAR6B inhibition leads to loss of TJ networks and membrane localization of aPKC but does not affect adherens junctions. CDC42 inhibition phenocopies PAR6B loss, confirming the requirement of the complete PAR6B-aPKC-CDC42-PAR3 complex for TJ formation. |
FISH amplicon analysis, siRNA knockdown, immunofluorescence, TJ network assay in MCF7 cells |
American journal of cancer research |
High |
22957302
|
| 2013 |
aPKC/Par-3/PARD6B expression domain at the apical/proximal region of cochlear hair cells is complementary and opposite to the Gαi3/mPins domain, defining two mutually exclusive polarity complexes that together control kinocilium migration and planar cell polarity; the aPKC/Par-3/Par-6b complex is non-overlapping with the core PCP protein Vangl2. |
Immunofluorescence co-localization in cochlear hair cells, genetic deletion of Gαi3/mPins, in vitro G-protein inhibition |
Nature cell biology |
Medium |
23934215
|
| 2014 |
RHO-ROCK signaling is required for segregation of apical (PARD6B, PRKCZ) and basal (SCRIB, LLGL1) polarity regulators in mouse blastomeres; ROCK inhibitor Y-27632 dampened this segregation and activated Hippo signaling, demonstrating that RHO-ROCK acts upstream of PARD6B apical localization in TE specification. |
Pharmacological inhibition (Y-27632, RHO GTPase inhibitor), immunofluorescence, YAP nuclear localization assay in mouse embryos |
Developmental biology |
Medium |
24997360
|
| 2015 |
PAK4 phosphorylates PARD6B at Ser143, blocking PARD6B's interaction with Cdc42; this provides a mechanism for controlling the subcellular localization of PARD6B and its interaction with other proteins downstream of Cdc42. |
In vitro kinase assay, site-directed mutagenesis (S143A), co-immunoprecipitation, cell-based localization in human bronchial epithelial cells |
The Biochemical journal |
High |
25662318
|
| 2015 |
TFAP2C (AP-2γ) regulates PARD6B expression in mouse embryos; TFAP2C depletion leads to downregulation of PARD6B, loss of apical cell polarity, F-actin disorganization, and activation of Hippo signaling in outer blastomeres. Rescue with Pard6b mRNA restored cell polarity but only partially corrected Hippo signaling, positioning PARD6B downstream of TFAP2C but upstream of, but not solely responsible for, Hippo suppression. |
siRNA knockdown, mRNA rescue experiments, immunofluorescence in mouse embryos |
Development (Cambridge, England) |
High |
25858457
|
| 2016 |
CDC42 is required for apical localization of PARD6B in the pharyngeal endoderm; Cdc42 ablation causes loss of apical-basal polarity and loss of apical PARD6B, with impaired thyroid bud outgrowth and failure of SHROOM3-dependent apical constriction. |
Conditional Cdc42 knockout in mouse embryos, immunofluorescence |
Biology open |
Medium |
26772200
|
| 2017 |
PARD6B knockdown in lung adenocarcinoma cells promotes EMT and invasion; silencing of Pard6b (part of the PKCζ/Pard3/Pard6b complex) induces EMT markers, increases cell migration and invasion, and promotes in vivo colonization. Human lung adenocarcinoma tissues express less Pard6b than adjacent normal tissue. |
siRNA knockdown, invasion assays, in vivo colonization model, gene expression profiling |
Cellular signalling |
Medium |
28652146
|
| 2017 |
PARD6B is required for apical recycling in polarized epithelial cells; RNAi screen identified PARD6B as necessary for FcRn-mediated transcytosis, and pulse-chase kinetic assays showed a strong dependence on PARD6B for apical (but not basolateral) recycling, implicating PARD6B in assembly or maintenance of the apical endosomal system. |
High-throughput RNAi screen, pulse-chase kinetic transport assays, transcytosis assays in polarized epithelial cells |
The Journal of cell biology |
High |
28069747
|
| 2017 |
Disrupting the interaction between PRKCZ (aPKCζ) and PARD6B in prostate progenitor cells is sufficient to randomize mitotic spindle orientation and expand the luminal compartment, recapitulating the spindle and cell lineage phenotypes seen with GATA3 loss. |
Dominant-interfering constructs disrupting PRKCZ-PARD6B interaction, immunofluorescence, lineage analysis in mouse prostate |
Stem cell reports |
Medium |
28285879
|
| 2018 |
HIPPO signaling (via YAP1/WWTR1) antagonizes apical localization of Par complex components PARD6B and aPKC in mouse embryos, creating a negative feedback loop; this repositions cells to the interior independently of Sox2 regulation, ensuring robust lineage segregation. |
Genetic loss-of-function (Yap1/Wwtr1 mutants), immunofluorescence, cell tracking in mouse embryos |
eLife |
High |
30526858
|
| 2018 |
In pleural mesothelial cells, increased Lgl1 competes with PAR-3A for binding to aPKC and PAR-6B, displacing PAR-3A from the PAR complex and causing cell polarity loss; Lgl1 siRNA prevents this polarity loss and Lgl1 conditional knockout attenuates pleural fibrosis in mice. |
Co-immunoprecipitation (Lgl1/aPKC/PAR-6B/PAR-3A), siRNA knockdown, conditional knockout mouse model |
Biochimica et biophysica acta. Molecular cell research |
Medium |
29842893
|
| 2022 |
In response to entry of certain viruses and bacterial toxins via the apical membrane, PARD6B and aPKC (components of the PARD6B-aPKC-Cdc42 apical polarity complex) undergo rapid proteasome-dependent degradation initiated by perturbation of apical membrane glycosphingolipids; loss of PARD6B depletes apical endosome function, rendering cells resistant to further apical infection—a form of cell-autonomous host defense. |
Virus/toxin treatment of polarized epithelial cells, proteasome inhibitor rescue, PARD6B knockout, apical endosome functional assays |
Cell host & microbe |
High |
35143768
|
| 2025 |
The PAR3-PARD6B-PRKCI complex is required for alveolar type II epithelial cell (AEC2) self-renewal; reduced PARD6B in emphysematous COPD arrests AEC2s in G0-G1 phase, impairing self-proliferation. Co-immunoprecipitation and mass spectrometry confirmed the trimeric complex, and 3D spheroid formation by primary mouse AEC2s validated the proliferative role. |
Bioinformatics of patient samples, in vitro smoke-injury models, viral transfection, co-immunoprecipitation + mass spectrometry, 3D spheroid formation with primary mouse AEC2s |
Stem cell research & therapy |
Medium |
40001200
|
| 2025 |
PARD6B promotes colorectal cancer cell proliferation and cell cycle progression by upregulating MYC expression through suppression of miR-34c (which directly targets and represses MYC); in vitro and in vivo experiments confirmed the PARD6B→miR-34c→MYC axis. |
In vitro knockdown/overexpression, in vivo xenograft, in silico pathway analysis, miR-34c functional assays |
Cancer science |
Medium |
40533910
|