Vinexin, CAP/ponsin, ArgBP2: A Novel Adaptor Protein Family Regulating Cytoskeletal Organization and Signal Transduction.

Kioka, Noriyuki; Ueda, Kazumitsu; Amachi, Teruo

doi:10.1247/csf.27.1

Cited by 190 publications

(233 citation statements)

References 54 publications

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“…To construct FLAG-tagged lp-dlg deletion mutants (644 -909, 842-909, 842-879, and 880 -909), the corresponding region of lp-dlg was amplified by PCR and subcloned into p401F. In vitro binding assays were performed as described previously (12). In brief, COS-7 cells were transiently transfected with various FLAGtagged constructs and washed twice with phosphate-buffered saline and lysed in Triton lysis buffer (1% Triton X-100, 100 g/ml p-amidinophenylmethanesulfonyl fluoride hydrochloride, 10 g/ml aprotinin, 10 g/ml leupeptin).…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…At LM and EM levels, reggies/flotillins co-cluster with various specific surface proteins and intracellular signal transduction components like the cellular prion protein (PrP C ), Thy-1, activated cell adhesion molecules (CAMs), Src family kinases (e.g. lck and fyn) and interact with actin cytoskeleton-associated protein (vinexins, CAP/ponsin and ArgBP2) [6,9,10,[13][14][15][16]. The induction of signal cascades is demonstrated by the elevation of intracellular Ca 2+ and MAP kinase phosphorylation during PrP C capping in T cells [10], by actin cytoskeletal changes [9,13,15,16] and by relocation of glucose transporter 4 to the plasma membrane in adipocytes [9].…”

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confidence: 99%

“…lck and fyn) and interact with actin cytoskeleton-associated protein (vinexins, CAP/ponsin and ArgBP2) [6,9,10,[13][14][15][16]. The induction of signal cascades is demonstrated by the elevation of intracellular Ca 2+ and MAP kinase phosphorylation during PrP C capping in T cells [10], by actin cytoskeletal changes [9,13,15,16] and by relocation of glucose transporter 4 to the plasma membrane in adipocytes [9]. Additional lines of evidence such as co-immunoprecipitation, cross-linking and microscopy confirm the idea that reggie/ flotillin microdomains play an important role in cell-cell recognition, adhesion and signaling events [reviewed in refs.…”

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confidence: 99%

Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain

Rivera-Milla

Stuermer

Málaga-Trillo

2006

Cell. Mol. Life Sci.

148

150

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Abstract. Reggies (flotillins) are detergent-resistant microdomains involved in the scaffolding of large heteromeric complexes that signal across the plasma membrane. Based on the presence of an evolutionarily widespread motif, reggies/flotillins have been included within the SPFH (stomatin-prohibitin-flotillin-HflC/K) protein superfamily. To better understand the origin and evolution of reggie/flotillin structure and function, we searched databases for reggie/flotillin and SPFH-like proteins in organisms at the base and beyond the animal kingdom, and used the resulting dataset to compare their structural Cell. Mol. Life Sci. 63 (2006) 343-357 1420-682X/06/030343-15 DOI 10.1007/s00018-005-5434-3 © Birkhäuser Verlag, Basel, 2006 and functional domains. Our analysis shows that the SPFH grouping has little phylogenetic support, probably due to convergent evolution of its members. We also find that reggie/flotillin homologues are highly conserved among metazoans but are absent in plants, fungi and bacteria, where only proteins with 'reggie-like' domains can be found. However, despite their low sequence similarities, reggie/flotillin and 'reggie-like' domains appear to subserve related functions, suggesting that their basic biological role was acquired independently during evolution.

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“…Furthermore, ERK is well known to be activated by integrin engagement and to be localized to adhesion sites (7, 10 -14). Although some cytoplasmic proteins, including myosin light chain kinase (MLCK), integrin ␤ subunits, and paxillin, have been reported to mediate the ERK-dependent stimulation of cell motility or cell adhesion (5,6,(15)(16)(17), details of the function of ERK or its substrates at adhesion sites remain to be determined.Vinexin was identified as a binding partner of vinculin, one of the major focal adhesion proteins (18,19). Vinexin is localized at focal adhesion sites as well as cell-cell contact sites.…”

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confidence: 99%

Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin

Mitsushima

Suwa

Amachi

et al. 2004

Journal of Biological Chemistry

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Extracellular signal-regulated kinase 1/2 (ERK1/2) is activated by various extracellular stimuli including growth factors and cytokines and plays a pivotal role in regulating cell proliferation and differentiation by phosphorylating nuclear transcription factors. Recently, it was reported that activated ERK1/2 also concentrates at adhesion sites and regulates cell spreading and migration. Vinexin is a focal adhesion protein regulating both cell spreading and growth factor signaling. We show here that vinexin was directly phosphorylated by ERK1/2 upon stimulation with growth factors. ERK1/2 phosphorylated the linker region of vinexin between the second and third SH3 domains. Site-directed mutagenesis revealed that ERK2 mainly phosphorylated the serine 189 residue of vinexin ␤. Furthermore, vinexin ␤ interacted with ERK1/2 both in vitro and in vivo. Vinexin interacted with the active but not inactive form of ERK1/2. A putative DEF (docking for ERK FXFP) domain located in the linker region of vinexin was required for the interaction with ERK1/2 and efficient phosphorylation of vinexin ␤ by ERK2. Finally, we showed that cell adhesion to fibronectin also induced the association of vinexin ␤ with ERK2 and the phosphorylation of vinexin ␤. Furthermore, vinexin and ERK were co-localized to the periphery of cells during cell spreading on fibronectin. Together, these results suggest that vinexin is a novel substrate of ERK2 and may play roles in ERK-dependent cell regulation during cell spreading as well as in growth factor-induced responses.Mitogen-activated protein kinase (MAPK) 1 consists of four subfamilies, extracellular signal-regulated kinase 1/2 (ERK1/ 2), c-Jun N-terminal kinase/stress-activated kinase, p38MAPK, and ERK5. ERK1/2 is mainly activated by various growth factors and regulates a diverse array of cellular events including cell proliferation, survival, and differentiation (1, 2). Many extracellular signals activate membrane receptors, including receptor tyrosine kinases, G protein-coupled receptors, or integrins, leading to the activation of Raf. Activated Raf, in turn, activates MEK (MAPK/ERK kinase) by the direct phosphorylation of dual serine residues. Activated MEK also directly phosphorylates and activates ERK1/2. Once activated, ERK1/2 enters the nucleus and phosphorylates nuclear transcription factors, including Elk-1, Sap1, c-Myc, and c-Fos (3).Recently, ERK has been shown to play crucial roles in regulating cell adhesion and cell migration independent of its nuclear functions (4 -7). ERK is involved in the migration of breast cancer cells stimulated by urokinase-type tissue plasminogen activator. Neither de novo gene transcription nor protein synthesis is required for this process (5). Activation of ERK is also suggested to be involved in the chemotaxis or the extension of pseudopodia, probably through the phosphorylation of cytoplasmic proteins (8, 9). Furthermore, ERK is well known to be activated by integrin engagement and to be localized to adhesion sites (7, 10 -14). Although some cytoplasm...

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Vinexin, CAP/ponsin, ArgBP2: A Novel Adaptor Protein Family Regulating Cytoskeletal Organization and Signal Transduction.

Cited by 190 publications

References 54 publications

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

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

Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain

Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin

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