Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3

Traweger, Andreas; Wiggin, Giselle R.; Taylor, Lauren J.; Tate, Stephen; Metalnikov, Pavel; Pawson, Tony

doi:10.1073/pnas.0804102105

Cited by 76 publications

(64 citation statements)

References 34 publications

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“…A large body of evidence shows that interference in the interactions between TJ proteins perturbs the TJs affecting the barrier permeability of the endothelium ( 38 ). It was further observed that the TJ formation or disintegration depends on the phosphorylation state of TJ proteins (39)(40)(41). However, most of these studies were focused on epithelial TJs, and therefore, the role of phosphorylation of TJ proteins in the preservation or perturbation of endothelial TJ integrity and its barrier function has not been well-studied.…”

Section: Xo-dependent Ros Production Mediates 15(s)-heteinduced Jama mentioning

confidence: 99%

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Chattopadhyay

Tinnikov

Dyukova

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org surface to the circulating blood, and releases vasoactive substances involved in the regulation of vascular tone ( 1, 2 ). Besides, it selectively permits the movement of molecules into and out of the bloodstream, and this semipermeable capacity of the endothelial monolayer depends majorly on cell-to-cell connections, namely adherens junctions (AJs), tight junctions (TJs), and gap junctions ( 3, 4 ). Disruption of these junctions leads to a leaky endothelial barrier, which allows the traffi cking of leukocytes through the blood vessels into the interstitial space and initiates infl ammation ( 2, 4 ). A large body of evidence indicates that TJs of endothelium play a pivotal role in modulating its barrier permeability, and dysfunctional endothelium often manifests increased barrier permeability ( 5, 6 ). Many studies suggest that oxidative stress is one of the underlying factors in endothelial dysfunction and atherosclerosis ( 7,8 ). NADPH oxidase, a major source of reactive oxygen species (ROS) production ( 9 ), has been reported to increase EC barrier permeability ( 10, 11 ). Xanthine oxidase (XO), a purine-catabolizing enzyme, was also found as another major source of cellular ROS production ( 12 ). XO results from sulfhydryl oxidation or proteolytic conversion of xanthine dehydrogenase (XDH) ( 13,14 ). Although both XDH and XO convert hypoxanthine and xanthine to uric acid, XO preferentially converts molecular oxygen to superoxide anion and hydrogen peroxide ( 12 ). However, under the reduced state, XDH can also react with molecular oxygen and generate ROS ( 15 ). Although the physiological signifi cance of XDH conversion to XO is not clear, XO was found to be abundantly present in several tissues, including in the luminal surface of the microvascular endothelium, and is thought to be involved in the pathogenesis of various diseases such as infl ammation and Endothelium, which is constituted by a monolayer of endothelial cells (ECs), is the inner most lining of the blood vessels, provides nonplatelet adherent nonthrombotic Abstract To understand the mechanisms of 15(S)-HETEinduced endothelial cell (EC) barrier dysfunction, we examined the role of xanthine oxidase (XO). 15(S)-HETE induced

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Section: Xo-dependent Ros Production Mediates 15(s)-heteinduced Jama mentioning

confidence: 99%

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Chattopadhyay

Tinnikov

Dyukova

et al. 2015

Journal of Lipid Research

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“…The Aurora A phosphorylation site is located close to the Par3-aPKCBC. This region of Par3 contains the binding sites for aPKC, Kif3A, Tiam-1, Stef, Mark2, and Numb (17,18,33,(37)(38)(39)(40)(41). However, preliminary results show that Aurora A phosphorylation does not affect the binding of these proteins.…”

Section: Discussionmentioning

confidence: 61%

Phosphorylation of the Par Polarity Complex Protein Par3 at Serine 962 Is Mediated by Aurora A and Regulates Its Function in Neuronal Polarity

Khazaei¹,

Püschel

2009

Journal of Biological Chemistry

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The Aurora kinases are a family of serine/threonine protein kinases that perform important functions during the cell cycle. Recently, it was shown that Drosophila Aurora A also regulates the asymmetric localization of Numb to the basal and the partitioning-defective (Par) complex to the apical cortex of neuroblasts by phosphorylating Par6. Here, we show that Aurora A is required for neuronal polarity. Suppression of Aurora A by RNA interference results in the loss of neuronal polarity. Aurora A interacts directly with the atypical protein kinase C binding domain of Par3 and phosphorylates it at serine 962. The phosphorylation of Par3 at serine 962 contributes to its function in the establishment of neuronal polarity.

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“…It has been previously reported that PAR-3 occasionally localizes to the nucleus, as well as to cell-cell contacts (Fang et al, 2007). Biochemical studies indicated that PAR-3 can form a complex with the Ku80, Ku70 and catalytic subunits of DNA-dependent protein kinase (DNA-PK), which are also AP-2-binding proteins (Fang et al, 2007;Nolens et al, 2009;Traweger et al, 2008). Thus, PAR-3 might activate Girdin transcription by binding to the DNA-PK-AP-2 complex, and aPKC might be involved in processes such as protein assembly.…”

Section: Regulation Of Girdin Transcription By the Par-3 Cell Polaritmentioning

confidence: 99%

Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin–Gαi3 signaling

Sasaki

Kakuwa

Akimoto

et al. 2015

Journal of Cell Science

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Epithelial apicobasal polarity has fundamental roles in epithelial physiology and morphogenesis. The PAR complex, comprising PAR-3, PAR-6 and aPKC, is involved in determining cell polarity in various biological contexts, including in epithelial cells. However, it is not fully understood how the PAR complex induces apicobasal polarity. In this study, we show that PAR-3 regulates the protein expression of Girdin (GIV/CCDC88A), a guanine nucleotide exchange factor (GEF) for heterotrimeric Gαi subunits, at the transcriptional level by cooperating with the AP-2 transcription factor. In addition, we confirmed that PAR-3 physically interacts with Girdin, and show that Girdin, together with the Gαi3, controls tight junction formation, apical domain development and actin organization downstream of PAR-3. Taken together, our findings suggest that transcriptional upregulation of Girdin and Girdin–Gαi3 signaling play crucial roles in regulating epithelial apicobasal polarity via the PAR complex.

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Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3

Cited by 76 publications

References 34 publications

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Phosphorylation of the Par Polarity Complex Protein Par3 at Serine 962 Is Mediated by Aurora A and Regulates Its Function in Neuronal Polarity

Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin–Gαi3 signaling

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