Protein Kinase C Regulates the Phosphorylation and Cellular Localization of Occludin

Andreeva, Anna; Krause, Eberhard; Müller, Eva; Blasig, Ingolf E.; Utepbergenov, Darkhan

doi:10.1074/jbc.m104923200

Cited by 184 publications

(165 citation statements)

References 34 publications

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“…After washing three times with PBS, 0.5% Triton X-100, bound proteins were eluted with Laemmli buffer (eluate). Eluate and unbound fractions were analyzed by SDS-PAGE and Western blot as described previously (26).…”

Section: Measurements Of Transepithelial Electrical Resistance (Teer)mentioning

confidence: 99%

Molecular Determinants of the Interaction between Clostridium perfringens Enterotoxin Fragments and Claudin-3

Winkler¹,

Gehring

Wenzel

et al. 2009

Journal of Biological Chemistry

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108

144

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Section: Measurements Of Transepithelial Electrical Resistance (Teer)mentioning

confidence: 99%

Molecular Determinants of the Interaction between Clostridium perfringens Enterotoxin Fragments and Claudin-3

Winkler¹,

Gehring

Wenzel

et al. 2009

Journal of Biological Chemistry

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108

144

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“…In non-epithelial cells ZO-1 is a major component of AJ, whereas in epithelial cells it is localized at TJ by directly binding to claudins (6). Occludin, one of the transmembrane proteins of TJ, is a multiphosphoprotein involved in regulation of TJ (7). It has four transmembrane domains with two extracellular loops and a cytosolic N and C terminus.…”

mentioning

confidence: 99%

The Tight Junction Protein Occludin and the Adherens Junction Protein α-Catenin Share a Common Interaction Mechanism with ZO-1

Müller

Portwich

Schmidt

et al. 2005

Journal of Biological Chemistry

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149

150

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The exact sites, structures, and molecular mechanisms of interaction between junction organizing zona occludence protein 1 (ZO-1) and the tight junction protein occludin or the adherens junction protein ␣-catenin are unknown. Binding studies by surface plasmon resonance spectroscopy and peptide mapping combined with comparative modeling utilizing crystal structures led for the first time to a molecular model revealing the binding of both occludin and ␣-catenin to the same binding site in ZO-1. Our data support a concept that ZO-1 successively associates with ␣-catenin at the adherens junction and occludin at the tight junction. Strong spatial evidence indicates that the occludin C-terminal coiled-coil domain dimerizes and interacts finally as a four-helix bundle with the identified structural motifs in ZO-1. The helix bundle of occludin 406 -521 and ␣-catenin Different junctional complexes such as adherens junctions and, in specialized tissues, tight junctions, gap junctions, and desmosomes connect cells in multicellular organisms. TJ 1 seal the most apical-lateral parts of cells and constitute a diffusion barrier for the paracellular flow of molecules and serve as a fence between the apical and basolateral membrane compartment (1). In contrast, AJ play important roles in cell adhesion, migration, morphogenesis, and proliferation. AJ represent Ca 2ϩ -dependent cell-cell contacts localized basolateral of TJ, where transmembrane proteins of the cadherin family mediate adhesion. Assembly of AJ is a prerequisite for the formation of TJ and desmosomes (2). ␤-and ␣-catenin bind to the cadherin cytoplasmic domain and link the cadherin-catenin complex to the F-actin cytoskeleton. An important scaffolding protein in cell-cell contacts is the zona occludens protein 1. ZO-1 is a membrane associated guanylate kinase homologue protein composed of the following domains: three PDZ (PSD95/Dlg/ZO-1), a SH3, a GuK (3), an actin binding region (4), and a ZU5 (ZO-1 and Unc5-like netrin receptor domain) according SMART (Simple Modular Architecture Research Tool (smart.embl-heidelberg.de) data base (5)). In non-epithelial cells ZO-1 is a major component of AJ, whereas in epithelial cells it is localized at TJ by directly binding to claudins (6). Occludin, one of the transmembrane proteins of TJ, is a multiphosphoprotein involved in regulation of TJ (7). It has four transmembrane domains with two extracellular loops and a cytosolic N and C terminus. A sequence of 244 amino acids in human ZO-1 containing the GuK domain and an acidic region C terminus to GuK binds to the complete intracellular C-terminal tail of chicken occludin (8).ZO-1 also binds to the AJ protein ␣-catenin (9) and to connexins in gap junctions (10), indicating a general scaffolding function of ZO-1 in junctional complexes. ␣-Catenin consists of several four-helix-bundle domains (vinculin homology domains, VH1-3) and binds ␤-catenin via an intermolecular helix bundle mechanisms within the E-cadherin-catenin complex at the intracellular side of AJ, where one helix of ...

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“…More recently, nitric oxide (NO) and Ca 2ϩ have been shown to partially mediate the effects of H and H/R on cellular permeability, though the mechanisms by which NO and Ca 2ϩ may cause these permeability changes are still unclear (17, 35). However, it has recently been suggested that phosphorylation of the TJ proteins can affect the functionality of the TJ (4,23,33,46). Several intracellular signaling molecules have been shown to regulate TJ protein phosphorylation, including tyrosine kinases, MAPK, and PKC (4,33).…”

mentioning

confidence: 99%

“…However, it has recently been suggested that phosphorylation of the TJ proteins can affect the functionality of the TJ (4,23,33,46). Several intracellular signaling molecules have been shown to regulate TJ protein phosphorylation, including tyrosine kinases, MAPK, and PKC (4,33).…”

mentioning

confidence: 99%

Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation

Fleegal

Hom

Borg

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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-The blood-brain barrier (BBB) is a metabolic and physiological barrier important for maintaining brain homeostasis. The aim of this study was to determine the role of PKC activation in BBB paracellular permeability changes induced by hypoxia and posthypoxic reoxygenation using in vitro and in vivo BBB models. In rat brain microvessel endothelial cells (RMECs) exposed to hypoxia (1% O 2-99% N2; 24 h), a significant increase in total PKC activity was observed, and this was reduced by posthypoxic reoxygenation (95% room air-5% CO 2) for 2 h. The expression of PKC-␤II, PKC-␥, PKC-, PKC-, and PKC-also increased following hypoxia (1% O 2-99% N2; 24 h), and these protein levels remained elevated following posthypoxic reoxygenation (95% room air-5% CO 2; 2 h). Increases in the expression of PKC-⑀ and PKC-were also observed following posthypoxic reoxygenation (95% room air-5% CO 2; 2 h). Moreover, inhibition of PKC with chelerythrine chloride (10 M) attenuated the hypoxiainduced increases in [ 14 C]sucrose permeability. Similar to what was observed in RMECs, total PKC activity was also stimulated in cerebral microvessels isolated from rats exposed to hypoxia (6% O 2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min). In contrast, hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min) significantly increased the expression levels of only PKC-␥ and PKC-in the in vivo hypoxia model. These data demonstrate that hypoxia-induced BBB paracellular permeability changes occur via a PKC-dependent mechanism, possibly by differentially regulating the protein expression of the 11 PKC isozymes. protein kinase C; paracellular; neurovascular unit; rat THE BLOOD-BRAIN BARRIER (BBB) is a metabolic and physiological barrier important for maintaining cerebral homeostasis. Brain microvessels that form the BBB are lined with specialized endothelial cells surrounded by pericytes, astroglial processes, and the extracellular matrix. Compared with the peripheral microvasculature, cerebral microvessels are highly specialized because they lack vesicular transport and fenestrations while having a high level of metabolic activity. This lack of fenestrations is due to the presence of tight junctions (TJ) and adherens junctions, which restrict paracellular movement of molecules across the BBB (29,31,40).Stroke is a leading cause of death and disability in the United States (3). It has been demonstrated that the BBB is compromised during stroke (29). The effects of stroke on the cerebral vasculature significantly contribute to the brain damage caused by stroke. It has been determined that the lack of oxygen (hypoxia, H) followed by reperfusion (posthypoxic reoxygenation, H/R) during stroke contributes to both neuronal and vascular damage. Both H and H/R cause increases in cerebrovascular permeability with concomitant increases in vasogenic cerebral edema (1,36,47).Previous studies (36, 47) have demonstrated that H and H/R cause changes in paracellular permeability to [ 14 C]sucrose in cerebral vascular endothelial cells....

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Protein Kinase C Regulates the Phosphorylation and Cellular Localization of Occludin

Cited by 184 publications

References 34 publications

Molecular Determinants of the Interaction between Clostridium perfringens Enterotoxin Fragments and Claudin-3

Molecular Determinants of the Interaction between Clostridium perfringens Enterotoxin Fragments and Claudin-3

The Tight Junction Protein Occludin and the Adherens Junction Protein α-Catenin Share a Common Interaction Mechanism with ZO-1

Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation

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