Cell cycle-dependent activation of Ras

Taylor, Stephen J.; Shalloway, David

doi:10.1016/s0960-9822(02)70785-9

Cited by 370 publications

(298 citation statements)

References 26 publications

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“…We therefore examined whether Necl-5 enhanced the serum-induced activation of each component of this signaling. Consistent with earlier observations (28), serum induced activation of Ras, MEK, and ERK in wild-type NIH3T3 cells (Fig. 4B).…”

Section: Enhancement Of Cell Proliferation By Necl-5-we Havesupporting

confidence: 92%

Enhancement of Serum- and Platelet-derived Growth Factor-induced Cell Proliferation by Necl-5/Tage4/Poliovirus Receptor/CD155 through the Ras-Raf-MEK-ERK Signaling

Kakunaga

Ikeda

Shingai

et al. 2004

Journal of Biological Chemistry

108

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Necl-5/Tage4/poliovirus receptor/CD155 has been shown to be the poliovirus receptor and to be up-regulated in rodent and human carcinoma. We have found previously that mouse Necl-5 regulates cell motility. We show here that mouse Necl-5 is furthermore involved in the regulation of cell proliferation. Studies using a specific antibody against Necl-5 and a dominant negative mutant of Necl-5 revealed that Necl-5 enhanced the serum-induced proliferation of NIH3T3, Swiss3T3, and mouse embryonic fibroblast cells. Necl-5 enhanced the serum-induced activation of the Ras-Raf-MEK-ERK signaling, up-regulated cyclins D2 and E, and down-regulated p27 Kip1 Necl-5/Tage4/poliovirus receptor (PVR) 1 /CD155 is an immunoglobulin (Ig)-like molecule having a domain structure consisting of one extracellular region with three Ig-like loops, one transmembrane region, and one cytoplasmic region (1-4). Human PVR/CD155 was originally identified as the human PVR (1, 2), whereas rodent Tage4 was originally identified as the product of a gene overexpressed in rat and mouse colon carcinoma (3, 4). PVR/CD155 has also been shown to be overexpressed in human colorectal carcinoma and malignant glioma (5, 6). The PVR/CD155 gene has thus far been found only in the primates, and the Tage4 gene has thus far been found only in the rodent, but these genes are likely to be derived from the common ancestor gene (7,8) and tentatively renamed nectinlike molecule-5, Necl-5 (for a review, see Ref. 9). Nectin-like molecules (Necls) have been named for a group of Ig-like molecules whose domain structures are similar to, but slightly different from, those of nectins (9). Nectins are Ca 2ϩ -independent Ig-like cell-cell adhesion molecules that constitute a family of four members, nectin-1, -2, -3, and -4 (for reviews, see Refs. 9 and 10). Nectins form cis-dimers followed by formation of trans-dimers (trans-interaction), eventually causing cell-cell adhesion. Nectins first form cell-cell adhesion where cadherins are recruited, resulting in formation of adherens junctions in epithelial cells and fibroblasts. Nectins are associated with the actin cytoskeleton through afadin, a nectin-and actin filamentbinding protein, as cadherins are associated with the actin cytoskeleton through ␣-and ␤-catenins (for a review, see Ref. 11). Necl-5 is one member of the Necl family consisting of five members, Necl-1, -2, -3, -4, and -5 (9). Although they have domain structures similar to those of nectins, they do not directly bind afadin.Nectin-3 forms not only homo-trans-dimers but also heterotrans-dimers (heterophilic trans-interaction) with either nectin-1 or -2 (9, 10). Nectin-4 forms hetero-trans-dimers with nectin-1, but nectin-1 does not form hetero-trans-dimers with nectin-2. These hetero-trans-dimers show much higher cell-cell adhesion activity than the homo-trans-dimers. In contrast to nectins, Necl-5 does not show homophilic cell-cell adhesion activity (12, 13). Thus, the role of Necl-5 as the PVR has been established, but its physiological role remained unknown for a...

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Section: Enhancement Of Cell Proliferation By Necl-5-we Havesupporting

confidence: 92%

Enhancement of Serum- and Platelet-derived Growth Factor-induced Cell Proliferation by Necl-5/Tage4/Poliovirus Receptor/CD155 through the Ras-Raf-MEK-ERK Signaling

Kakunaga

Ikeda

Shingai

et al. 2004

Journal of Biological Chemistry

108

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“…The in vivo studies showing tight control of DGK␣ during T cell activation suggest that, as is the case for other signaling molecules in T lymphocytes (19,20), DGK␣ expression is coupled to cell cycle progression. The complex regulation of DGK␣ during in vivo T cell activation is probably a consequence of the distinct role of this enzyme at different stages during T lymphocyte activation and proliferation.…”

Section: Discussionmentioning

confidence: 93%

T Cell Activation In Vivo Targets Diacylglycerol Kinase α to the Membrane: A Novel Mechanism for Ras Attenuation

Sanjuán

Pradet‐Balade

Jones

et al. 2003

The Journal of Immunology

110

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Diacylglycerol kinase (DGK) phosphorylates diacylglycerol to produce phosphatidic acid, leading to decreased and increased levels, respectively, of these two lipid messengers that play a central role in T cell activation. Nine DGK isoforms, grouped into five subtypes, are found in higher organisms; all contain a conserved C-terminal domain and at least two cysteine-rich motifs of unknown function. In this study, we have researched in vivo the regulation of DGKα, using a transgenic mouse model in which injection of an antigenic peptide activates the majority of peripheral T cells. We demonstrate that DGKα, highly expressed in resting T lymphocytes, is subject to complex control at the mRNA and protein levels during in vivo T cell activation. Subcellular fractionation of T lymphocytes shortly after in vivo engagement of the TCR shows rapid translocation of cytosolic DGKα to the membrane fraction. At early time points, DGKα translocation to the membrane correlates with rapid translocation of Ras guanyl nucleotide-releasing protein (RasGRP), a nucleotide exchange activator for Ras that associates to the membrane through a diacylglycerol-binding domain. To demonstrate a causal relationship between DGKα activity and RasGRP relocation to the membrane, we determined RasGRP translocation kinetics in a T cell line transiently transfected with constitutive active and dominant-negative DGKα mutants. We show that membrane localization of DGKα is associated with a negative regulatory signal for Ras activation by reversing RasGRP translocation. This study is the first demonstration of in vivo regulation of DGKα, and provides new insight into the functional role of a member of this family of lipid kinases in the regulation of the immune response.

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“…Assaying the Activation of Cdc42 in Cells Using the Limit Cdc42/Racbinding Domain from PAK-Activation of cellular Cdc42 was assayed as previously described (11,28), based on a procedure originally developed for Ras (29). COS-7 cells were transiently transfected with the cDNA for wild-type Cdc42 in the pcDNA3 vector.…”

Section: Methodsmentioning

confidence: 99%

Epidermal Growth Factor-dependent Regulation of Cdc42 Is Mediated by the Src Tyrosine Kinase

Wang

et al. 2003

Journal of Biological Chemistry

102

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Cdc42 is a member of the Rho subfamily of Ras-related GTP-binding proteins and has been implicated in a wide range of cellular processes and signaling activities. Among its best known actions is the regulation of actin cytoskeletal architecture, because microinjection of activated Cdc42 was found to give rise to filopodia formation, whereas the closely related Rac and RhoA proteins were implicated in membrane ruffling and in the generation of actin stress fibers, respectively (1-4). A number of lines of evidence have also implicated Cdc42 in the control of normal cell growth and, when hyperactivated, in cellular transformation. These include the findings that Dbl (for diffuse B cell lymphoma) and a number of related guanine nucleotide exchange factors (GEFs) 1 for Cdc42 and other Rho proteins are capable of transforming cells and that mutations in Cdc42 that mimic the actions of GEFs and allow the spontaneous exchange of GDP for GTP exhibit oncogenic activity (5-10).

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Cell cycle-dependent activation of Ras

Cited by 370 publications

References 26 publications

Enhancement of Serum- and Platelet-derived Growth Factor-induced Cell Proliferation by Necl-5/Tage4/Poliovirus Receptor/CD155 through the Ras-Raf-MEK-ERK Signaling

Enhancement of Serum- and Platelet-derived Growth Factor-induced Cell Proliferation by Necl-5/Tage4/Poliovirus Receptor/CD155 through the Ras-Raf-MEK-ERK Signaling

T Cell Activation In Vivo Targets Diacylglycerol Kinase α to the Membrane: A Novel Mechanism for Ras Attenuation

Epidermal Growth Factor-dependent Regulation of Cdc42 Is Mediated by the Src Tyrosine Kinase

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