Another Ras-activated signaling pathway is the PI3K/AKT/mTOR pathway, which stimulates protein synthesis and cellular growth, and inhibits apoptosis. (wikipedia.org)
Intracellular4
Ras proteins function as binary molecular switches that control intracellular signaling networks. (wikipedia.org)
Inhibition of R-Ras/R-Ras2 and ROCK1 signaling also triggered the accumulation of abnormal intracellular vesicles, indicating that these signaling molecules regulate the movement of proteins and other molecules in the cellular interior. (biomedcentral.com)
Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. (frontiersin.org)
Despite its small genome and limited number of effector proteins, Ehrlichia efficiently establishes an intracellular infection and avoids immune defenses in vertebrate and invertebrate hosts through complex molecular and cellular reprogramming strategies. (frontiersin.org)
Pathways4
Ras activates several pathways, of which the mitogen-activated protein (MAP) kinase cascade has been well-studied. (wikipedia.org)
R-Ras proteins function distinctly from classic Ras proteins by regulating distinct signaling pathways that promote MPNST tumorigenesis by mediating migration and invasion. (biomedcentral.com)
We have previously shown that three related Ras proteins (the classic Ras proteins) are highly activated in malignant peripheral nerve sheath tumor (MPNST) cells with neurofibromin loss and that they drive cancer cell proliferation and survival by activating multiple cellular signaling pathways. (biomedcentral.com)
We examined the activation of cytoplasmic signaling pathways in the presence and absence of R-Ras signaling and found that R-Ras proteins regulated 13 signaling pathways distinct from those regulated by classic Ras proteins. (biomedcentral.com)
Subset2
R-Ras2 was uniformly expressed in MPNST cells, with R-Ras present in a major subset. (biomedcentral.com)
Instead, a specific subset of ISGs that includes Parp9 remains activated by the unphosphorylated form of ISGF3 that enhances nDNA damage and repair responses. (regenerativemedicine.net)
Proliferation4
We have shown that classic Ras proteins promote proliferation and survival, but not migration, in malignant peripheral nerve sheath tumor (MPNST) cells. (biomedcentral.com)
We assessed the expression and activation of these proteins in MPNST cells and inhibited them to determine the effect this had on proliferation, migration, invasion, survival and the phosphoproteome. (biomedcentral.com)
Consistent with classical Ras inhibition, DN R-Ras and R-Ras2 knockdown inhibited proliferation. (biomedcentral.com)
Inhibition of R-Ras action inhibited proliferation, migration and invasion but not survival. (biomedcentral.com)
Mutations3
Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. (wikipedia.org)
mutations that permanently activate Ras are found in 20 to 25% of all human tumors and up to 90% in certain types of cancer (e.g., pancreatic cancer). (wikipedia.org)
Mutations of the NF1 gene potentially results in the activation of multiple Ras proteins, which are key regulators of many biologic effects. (biomedcentral.com)
Promotes2
Loss of the Ras GTPase-activating protein neurofibromin promotes nervous system tumor pathogenesis in patients with neurofibromatosis type 1 (NF1). (biomedcentral.com)
We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)
Regulate1
Ras is the prototypical member of the Ras superfamily of proteins, which are all related in three-dimensional structure and regulate diverse cell behaviours. (wikipedia.org)
Survival2
When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. (wikipedia.org)
However, DN R-Ras inhibition impaired migration and invasion but not survival. (biomedcentral.com)
Cellular3
All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). (wikipedia.org)
Mass spectrometry-based phosphoproteomics identified thirteen protein networks distinctly regulated by DN R-Ras, including multiple networks regulating cellular movement and morphology. (biomedcentral.com)
Closer study of an R-Ras regulated pathway containing the signaling protein ROCK1 showed that inhibition of either R-Ras, R-Ras2 or ROCK1 similarly impaired cellular migration and invasion and altered cellular morphology. (biomedcentral.com)
Invasion1
Ras and Ras-related proteins are often deregulated in cancers, leading to increased invasion and metastasis, and decreased apoptosis. (wikipedia.org)
Networks1
Validation of R-Ras and R-Ras2 action and R-Ras regulated networks was performed using genetic and/or pharmacologic approaches. (biomedcentral.com)
Cells7
In 1982, activated and transforming human ras genes were discovered in human cancer cells by Geoffrey M. Cooper at Harvard, Mariano Barbacid and Stuart A. Aaronson at the NIH, Robert Weinberg at MIT, and Michael Wigler at Cold Spring Harbor Laboratory. (wikipedia.org)
A third ras gene was subsequently discovered by researchers in the group of Robin Weiss at the Institute of Cancer Research, and Michael Wigler at Cold Spring Harbor Laboratory, named NRAS, for its initial identification in human neuroblastoma cells. (wikipedia.org)
Cells were transfected with doxycycline-inducible vectors expressing either a pan-inhibitor of the R-Ras subfamily [dominant negative (DN) R-Ras] or enhanced green fluorescent protein (eGFP). (biomedcentral.com)
Proteins in cells with or without DN R-Ras expression were differentially labeled with SILAC and mass spectrometry was used to identify phosphoproteins and determine their relative quantities in the presence and absence of DN R-Ras. (biomedcentral.com)
Here, we examined the expression, activation and action of R-Ras proteins in MPNST cells that have lost neurofibromin. (biomedcentral.com)
Both R-Ras and R-Ras2 are expressed in MPNST cells and activated. (biomedcentral.com)
Results1
This cascade transmits signals downstream and results in the transcription of genes involved in cell growth and division. (wikipedia.org)
Expression1
Here, we find that persistent mtDNA stress is not associated with basally activated NF-κB signalling or interferon gene expression typical of an acute antiviral response. (regenerativemedicine.net)
Cancer3
Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. (wikipedia.org)
For this reason, Ras inhibitors are being studied as a treatment for cancer and other diseases with Ras overexpression. (wikipedia.org)
The first two Ras genes, HRAS and KRAS, were identified from studies of two cancer-causing viruses, the Harvey sarcoma virus and Kirsten sarcoma virus, by Edward M. Scolnick and colleagues at the National Institutes of Health (NIH). (wikipedia.org)
Differentiation2
When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. (wikipedia.org)
The Ras family of GTPases is a collection of molecular switches that link receptors on the plasma membrane to signaling pathways that regulate cell proliferation and differentiation. (embl.de)
Kinase3
It is known that the human Ras GTPase activating protein (GAP) p120-GAP can be phosphorylated by different members of the Src kinase family and recently phosphorylation of the GDP/GTP exchange factor (GEF) CDC25Mm/GRF1 by proteins of the Src kinase family has been revealed in vivo [Kiyono, M., Kaziro, Y. & Satoh, T. (2000) J. Biol. (embl.de)
In addition to its association with Ras, GAP has been shown to bind to several tyrosine-phosphorylated proteins in cells stimulated by growth factors or expressing transforming tyrosine kinase variants. (embl.de)
Microvesicles loaded with MCs encoding a thymidine kinase (TK)/nitroreductase (NTR) fusion protein produced prolonged TK-NTR expression in mammary carcinoma cells. (regenerativemedicine.net)
Hydrolysis3
The D is aspartate57, which is specific for guanine versus adenine binding, and Q is glutamine61, the crucial residue that activates a catalytic water molecule for hydrolysis of GTP to GDP. (wikipedia.org)
p120 GTPase-activating protein (GAP) down-regulates Ras by stimulating GTP hydrolysis of active Ras. (embl.de)
Apoptosis2
Ras and Ras-related proteins are often deregulated in cancers, leading to increased invasion and metastasis, and decreased apoptosis. (wikipedia.org)
Three alternatively spliced variants of mTid-1 were isolated, two of which correspond to the recently identified hTid-1(L) and hTid-1(S) forms of the human TID1 gene that exhibit opposing effects on apoptosis. (embl.de)
Phosphorylation3
The phosphorylation of p120-GAP by p60c-Src inhibited its ability to stimulate the Ha-Ras-GTPase activity, whereas phosphorylation by Lck did not display any effect. (embl.de)
phosphorylation by Lck increased its capacity to stimulate the GDP/GTP exchange on Ha-Ras, whereas its phosphorylation by p60c-Src was ineffective. (embl.de)
Our results suggest that phosphorylation by p60c-Src and Lck is a selective process that can modulate the activity of p120-GAP and CDC25Mm towards Ras proteins. (embl.de)
Human tumors2
mutations that permanently activate Ras are found in 20 to 25% of all human tumors and up to 90% in certain types of cancer (e.g., pancreatic cancer). (wikipedia.org)
Mutants of Ras are found in 25-30% of human tumors. (embl.de)
Amino acids2
The three human ras genes encode extremely similar proteins made up of chains of 188 to 189 amino acids. (wikipedia.org)
All known oncogenic mutants of Ras map to a small subset of amino acids. (embl.de)
Molecular2
This conformational change by the two switch motifs is what mediates the basic functionality as a molecular switch protein. (wikipedia.org)
Ras proteins function as binary molecular switches that control intracellular signaling networks. (wikipedia.org)
Homolog1
Here we report the cloning and characterization of a novel GAP-binding protein, mTid-1, a DnaJ chaperone protein that represents the murine homolog of the Drosophila tumor suppressor l(2)tid gene. (embl.de)
Involved in cell1
This cascade transmits signals downstream and results in the transcription of genes involved in cell growth and division. (wikipedia.org)
Cell4
Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. (wikipedia.org)
Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. (wikipedia.org)
Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. (wikipedia.org)
These results suggest that MC delivery via microvesicles can mediate gene transfer to an extent that enables effective prodrug conversion and tumor cell death such that it comprises a promising approach to cancer therapy. (regenerativemedicine.net)