The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42

Joberty, Gérard; Petersen, Clark; Gao, Lin; Macara, Ian G.

doi:10.1038/35019573

Cited by 870 publications

(890 citation statements)

References 37 publications

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“…PAR-3 has been implicated in the formation of normal tight junctions at epithelial cell-cell contacts (Joberty et al, 2000;Macara, 2004;Chen and Macara, 2005;Suzuki and Ohno, 2006). PAR-3 plays the role of a scaffold in the recruitment of proteins, such as PAR-6 or aPKC, that are involved in the formation of these junctions (Asse´mat et al, 2008).…”

Section: Analysis Of Pard3 Defects In Primary Tumorsmentioning

confidence: 99%

“…The mammalian homologs of the C. elegans polarity proteins have evolutionarily conserved functions in the establishment of cell polarity in various cell types. One of these homologs, PAR-3, contains one self-oligomerization domain in the N terminus, three PDZ protein interaction domains and one atypical protein kinase C (aPKC)-binding domain (Izumi et al, 1998;Joberty et al, 2000;Lin et al, 2000;Asse´mat et al, 2008). These domains enable PAR-3 to form a conserved protein complex with PAR-6 and aPKC (Macara, 2004;Suzuki and Ohno, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

et al. 2009

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The partition-defective 3 (PAR-3) protein is implicated in the formation of tight junctions at epithelial cell-cell contacts. We investigated DNA copy number aberrations in human esophageal squamous cell carcinoma (ESCC) cell lines using a high-density oligonucleotide microarray and found a homozygous deletion of PARD3 (the gene encoding PAR-3). Exogenous expression of PARD3 in ESCC cells lacking this gene enhanced the recruitment of zonula occludens 1 (ZO-1), a marker of tight junctions, to sites of cell-cell contact. Conversely, knockdown of PARD3 in ESCC cells expressing this gene caused a disruption of ZO-1 localization at cell-cell borders. A copy number loss of PARD3 was observed in 15% of primary ESCC cells. Expression of PARD3 was significantly reduced in primary ESCC tumors compared with their nontumorous counterparts, and this reduced expression was associated with positive lymph node metastasis and poor differentiation. Our results suggest that deletion and reduced expression of PARD3 may be a novel mechanism that drives the progression of ESCC.

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Section: Analysis Of Pard3 Defects In Primary Tumorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

et al. 2009

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“…It appears possible that the decreased release of NEFAs would permit the liver to suppress glucose production more efficiently under basal and insulin-stimulated conditions. To date, high levels of expression of human Par6α have only been verified in adult insulin-sensitive tissues, such as brain, liver, pancreas and skeletal muscle [22][23][24]. We have also recently demonstrated Par6α expression in the visceral adipose tissue of C57Bl6 mice (unpublished observation).…”

Section: Discussionmentioning

confidence: 79%

A novel functional polymorphism (?336A/G) in the promoter of the partitioning-defective protein-6? gene is associated with increased glucose tolerance and lower concentrations of serum non-esterified fatty acids

et al. 2005

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Aims/hypothesis: Partitioning-defective protein-6α (Par6α) has recently been demonstrated to negatively regulate insulin signalling in murine myoblasts. To address whether Par6α plays a role in human physiology, the present study investigated whether mutations exist in the Par6α gene and whether these mutations, if present, are associated with pre-diabetic phenotypes in non-diabetic subjects. Methods: The complete gene (part of the promoter [2.1 kb], all exons/introns and the 3′ untranslated region) encoding Par6α was analysed in 664 non-diabetic subjects. We investigated possible associations between single nucleotide polymorphisms and percentage of body fat, glucose tolerance (as determined by OGTT), serum NEFA concentrations and whole-body insulin sensitivity (estimated during the OGTT, and for a subgroup of 242 subjects determined by the euglycaemic-hyperinsulinaemic clamp). Results: A rare A/G polymorphism was found 336-bp upstream of the translational start codon (allele frequency 0.03). The data for subjects homozygous and heterozygous for −336G (R/G, n=43) were combined and compared with those for subjects homozygous for −336A (A/A, n=621). Subjects with the R/G genotype had lower fasting (4.84± 0.09 mmol/l, means±SEM, p=0.049) and 2-h (5.50±0.02 mmol/l, p=0.050) plasma glucose concentrations than subjects with the A/A genotype (5.02±0.02 and 5.94±0.06 mmol/l, respectively). Subjects with the R/G genotype also had lower fasting (448±31 μmol/l, p=0.018) and 2-h serum NEFA concentrations (61±7 μmol/l, p= 0.015) than subjects with the A/A genotype (529±9 and 75± 2 μmol/l, respectively), adjusted for age, sex and percentage of body fat. There were no differences in adiposity or whole-body insulin sensitivity between the two genotype groups (all p> 0.36). A luciferase reporter gene assay revealed that the −336G promoter variant had a significantly lower (−22.8%, p=0.006) transcriptional activity in transfected C2C12 murine myoblasts than the −336A promoter variant. Conclusions/interpretation: A novel functional variant in the promoter of the Par6α gene is associated with reduced fasting glycaemia, increased glucose tolerance and reduced serum NEFA concentrations.

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“…Par6α α α α is expressed in insulin-sensitive tissues of juvenile and adult C57/Bl6 mice Expression of Par6α has been reported in four insulin sensitive tissues (muscle, pancreas, liver, brain) by cloning or Northern blotting (Joberty et al, 2000;Johansson et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

The Par6α/aPKC complex regulates Akt1 activity by phosphorylating Thr34 in the PH-domain

Weyrich

Neuscheler

Melzer

et al. 2007

Molecular and Cellular Endocrinology

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Please cite this article as: Weyrich, P., Neuscheler, D., Melzer, M., Hennige, A.M., Häring, H.-U., Lammers, R., The Par6␣/aPKC complex regulates Akt1 activity by phosphorylating Thr34 in the PH-domain, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42

Cited by 870 publications

References 37 publications

Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

A novel functional polymorphism (?336A/G) in the promoter of the partitioning-defective protein-6? gene is associated with increased glucose tolerance and lower concentrations of serum non-esterified fatty acids

The Par6α/aPKC complex regulates Akt1 activity by phosphorylating Thr34 in the PH-domain

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