KATHLEEN JANEE GREEN

..We will explore signaling and trafficking machineries that drive assembly and remodeling and how these mechanisms are co-opted in human disease...

..Finally, we highlight the dynamic nature of these adhesive organelles, examining mechanisms in health and disease for modulating adhesive strength and stability of desmosomes...

..Our findings indicate that SERCA2-deficiency is sufficient to impede desmosome assembly and weaken intercellular adhesive strength via a PKCα-dependent mechanism, implicating SERCA2 as a novel regulator of PKCα signaling...

..These data provide direct in vitro evidence that IF-membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion...

..Remarkably, the data support a hypothesis that was presented more than 30 years ago...

..We end by discussing how mutations leading to defects in IF assembly, network formation or IF-IFAP association compromise in vivo functions of IF as protectors against environmental stress...

..Collectively, these observations demonstrate that Dsg1 promotes the formation of intercellular adhesion complexes and suggest that the relative level of Dsg and Dsc expressed at the cell surface regulates this adhesive process...

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..As a target for modulation by EGF, regulation of PG-dependent adhesion may play an important role during wound healing and tumor metastasis...

..These armadillo proteins participate in various nuclear functions, in some cases transducing signals regulating cell growth and differentiation...

..Our results suggest that EGFR inhibition promotes desmosome assembly in oral squamous cell carcinoma cells, resulting in increased cell-cell adhesion...

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..In addition to serving as a rigid anchor between adjacent cells, this study implicates desmosomal cadherins as key components of a signaling axis governing epithelial morphogenesis...

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..Here we will review the most recent data from our own group and others that are beginning to unveil the diverse properties and functions of this complex family of adhesion molecules...

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..Our analyses identify a novel role of p120 in promoting cell surface trafficking of cadherins via association and recruitment of kinesin...

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..These studies provide mechanistic insight into developing novel strategies for inhibiting prostate cancer cell motility and invasiveness...

..These findings further our understanding of the mechanism of exfoliative toxin-induced pathology and suggest novel strategies to suppress blistering in bulbous impetigo and staphylococcal scalded-skin syndrome...

..PKP2 knockdown is accompanied by increased phosphorylation of PKC substrates, raising the possibility that global alterations in PKC signaling may contribute to pathogenesis of congenital defects caused by PKP2 deficiency...

..IF networks can therefore be considered scaffolding upon which associated proteins are organized and regulated to control metabolic activities and maintain cell homeostasis...

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..Here, we describe the members of the plakin family and their interaction partners, and give examples of the cellular defects that result from their dysfunction...

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..Our data suggest that, in addition to plakoglobin, p0071 is the second armadillo protein present in both types of adhesive junctions and may play a role in regulating crosstalk between adherens junctions and desmosomes...

..These results suggest that p120ctn/plakophilin family proteins interact with intercellular junction binding partners to differentially modulate the adhesive and migratory behavior of epithelial cells...

..In contrast to the elongated structures formed by other kinds of repeat motifs, the plakin repeats form a globular structure with a unique fold. A conserved basic groove found on the domain may represent an IF-binding site...

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..The ability of apigenin to enhance UVB-induced apoptosis may explain, in part, the photochemopreventive effects of apigenin...

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..These data suggest DSP expression in cardiomyocytes is crucial for maintaining cardiac tissue integrity, and DSP abnormalities result in ARVD/C by cardiomyocyte death, changes in lipid metabolism, and defects in cardiac development...

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..These experiments promise to provide a model for the human disease striate palmoplantar keratoderma caused by loss of Dsg1, and will lay a foundation for developing treatments for skin diseases that target desmoglein function. ..

..These experiments promise to provide a model for the human disease striate palmoplantar keratoderma caused by loss of Dsg1, and will lay a foundation for developing treatments for skin diseases that target desmoglein function. ..

..Results from this work will also have important implications for the future tailoring of therapeutic strategies based on their cadherin and MMP status. ..

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..Results from this work will also have important implications for the future tailoring of therapeutic strategies based on their cadherin and MMP status. ..

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..This work should provide insights into the function of the PF antigen and may provide a groundwork for the development of a plasmapheresis-based therapy for PF...

..These experiments will lay the groundwork for understanding how desmosomes and the desmosome-IF attachment is established and how it may be perturbed in acquired and inherited pathologies. ..

..Funds are requested to support conference fees, and travel expenses of the participants. (ie. speakers, chairpersons, graduate students, and post docs. ..

..To examine the consequences of ectopically expressing Dsg1 or dominant negative plakoglobin mutants on adhesion, stratification and keratinocyte differention in organotypic raft cultures. ..