Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family

Dimitratos, Spiros D.; Woods, Daniel F.; Stathakis, Dean G.; Bryant, Peter J.

doi:10.1002/(sici)1521-1878(199911)21:11<912::aid-bies3>3.0.co;2-z

Cited by 201 publications

(129 citation statements)

References 87 publications

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“…The IKK complex is also phosphorylated in a PKC-dependent manner and both modifications are essential for the IKK kinase activity. MAGUK domain that is believed to link proteins to the cytoplasmic membrane [62]. The second step for CAR-MA1 recruitment to the immunological synapse seems to be dependent on its inducible interaction with an adaptor protein known as ADAP (adhesion-and degranulationpromoting adapter protein).…”

Section: The Mechanism Of T Cell Receptor-induced Car-ma1 Activationmentioning

confidence: 99%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

176

201

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The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

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Section: The Mechanism Of T Cell Receptor-induced Car-ma1 Activationmentioning

confidence: 99%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

176

201

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“…1A). PDZ domains are found in a variety of proteins, some of which localize at cell-cell junctions and function as scaffolding proteins (21,22), suggesting that vinexin may physiologically interact with this protein. Therefore, we focused on this clone in this study.…”

Section: Identification Of Lp-dlg/kiaa0583 As a Novel Vinexin Bindingmentioning

confidence: 99%

Interaction of lp-dlg/KIAA0583, a Membrane-associated Guanylate Kinase Family Protein, with Vinexin and β-Catenin at Sites of Cell-Cell Contact

Wakabayashi

Ito

Mitsushima

et al. 2003

Journal of Biological Chemistry

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Vinexin is a recently identified cytoskeletal protein and plays a key role in the regulation of cytoskeletal organization and signal transduction. Vinexin localizes at sites of cell-extracellular matrix adhesion in NIH3T3 fibroblasts and at sites of cell-cell contact in epithelial LLC-PK1 cells. Expression of vinexin promotes the formation of actin stress fiber, but the role of vinexin at sites of cell-cell contact is unclear. Here we identified lp-dlg/KIAA0583 as a novel binding partner for vinexin by using yeast two-hybrid screening. lp-dlg/KIAA0583 has a NH 2 -terminal coiled-coil-like domain, in addition to four PDZ domains, an Src homology (SH) 3 domain, and a guanylate kinase domain, which are conserved structures in membrane-associated guanylate kinase family proteins. The third SH3 domain of vinexin bound to the region between the second and third PDZ domain of lp-dlg, which contains a proline-rich sequence. lp-dlg colocalized with vinexin at sites of cell-cell contact in LLC-PK1 cells. Furthermore, lp-dlg colocalized with ␤-catenin, a major adherens junction protein, in LLC-PK1 cells. Co-immunoprecipitation experiments revealed that both endogenous and epitope-tagged deletion mutants of lp-dlg/KIAA0583 associated with ␤-catenin. We also showed that these three proteins could form a ternary complex. Together these findings suggest that lp-dlg/KIAA0583 is a novel scaffolding protein that can link the vinexin-vinculin complex and ␤-catenin at sites of cell-cell contact.Cell-cell adhesion is important for cell polarity, tissue morphogenesis development, and homeostasis (1-3). To this end, epithelial cells exhibit specialized structures involved in cell-cell contacts such as tight junctions and adherens junctions. Adherens junctions contain the transmembrane cell adhesion molecules, cadherins and nectins, which mediate the calcium-dependent and -independent cell-cell adhesion (1, 3, 4), respectively. The cytoplasmic domain of cadherin binds to ␤-catenin, which then binds to ␣-catenin. ␣-Catenin binds to actin and actin-binding proteins such as vinculin, ␣-actinin, and ZO-1, resulting in the link of cadherin to the actin cytoskeleton (3, 5, 6). The cytoplasmic domain of nectin binds to l-afadin, which then binds to actin and a vinculin-binding protein ponsin (4,7,8). Multiple protein complexes of these cytoplasmic proteins play important roles in communicating between cell adhesion systems, regulating cellcell adhesion, and transducing signals into cells.Vinexin is a protein localizing at cell-cell and cell-extracellular matrix junctions (9). There are at least two types of vinexin, vinexin ␣ and vinexin ␤, which share a common carboxyl-terminal sequence containing three SH (Src homology) 3 1 domains. The larger vinexin ␣ has an additional amino-terminal sequence containing a sorbin homology domain. Vinexin is a member of a novel adaptor protein family, including ArgBP2 and ponsin, all of which have a sorbin homology domain in the NH 2 -terminal half and three SH3 domains in the COOHterminal half (8 -12). Vin...

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“…pyd ectopic bristles are due to the formation of additional SMCs (Chen et al, 1996;Takahisa et al, 1996) which appear to result from reduced transcription of emc in pyd mutant discs (Takahisa et al, 1996). Pyd is a PDZ domain protein whose sequence is closely related to mammalian Zona occludens proteins ZO-1, ZO-2 and ZO-3, members of the membrane-associated guanylate kinase homologue (MAGUK) family (reviewed in Dimitratos et al, 1999). Since Pyd is associated with septate and adherens junctions (Takahisa et al, 1996;Wie and Ellis, 2001), its role in emc regulation cannot be a direct one.…”

Section: Regulation Of Transcription and Translation Of Emcmentioning

confidence: 99%

“…Since Pyd is associated with septate and adherens junctions (Takahisa et al, 1996;Wie and Ellis, 2001), its role in emc regulation cannot be a direct one. The presence of multiple protein ± protein interaction domains in PDZ proteins allows them to act as sca olding components to organize protein complexes (Dimitratos et al, 1999). Accordingly, it has been suggested that Pyd participates in a signaling pathway that ultimately activates emc expression (Takahisa et al, 1996).…”

Section: Regulation Of Transcription and Translation Of Emcmentioning

confidence: 99%

Emc, a negative HLH regulator with multiple functions in Drosophila development

Campuzano

2001

Oncogene

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Expression and functional analyses of Emc have demonstrated that it is a prototype for a protein required for multiple processes in development. Initially characterized as a negative regulator of sensory organ development, it was later found to regulate many other developmental processes and cell proliferation. Its ability to block the function of bHLH proteins by forming heterodimers, which are ine ective in DNA binding, accounts for the role of Emc in preventing the acquisition of several cell fates which are under the control of bHLH proteins. However, while maintaining this repressive molecular mechanism, emc also appears to act as a positive regulator of di erentiation. Oncogene (2001) 20, 8299 ± 8307

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Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family

Cited by 201 publications

References 87 publications

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Interaction of lp-dlg/KIAA0583, a Membrane-associated Guanylate Kinase Family Protein, with Vinexin and β-Catenin at Sites of Cell-Cell Contact

Emc, a negative HLH regulator with multiple functions in Drosophila development

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