Pathways effector proteins ras gtpase activating proteins. Medical search. Frequent questions

The intracellular/cytoplasmic region of the ErbB receptor consists mainly of three subdomains: A juxtamembrane with approximately 40 residues, a kinase domain containing approximately 260 residues and a C-terminal domain of 220-350 amino acid residues that become activated via phosphorylation of its tyrosine residues that mediates interactions of other ErbB proteins and downstream signaling molecules. (wikipedia.org)
The ability ('+') or inability ('-') of each growth factor to activate each of the ErbB receptors is shown in the table below: The dimerization occurs after ligand bind to the extracellular domain of the ErbB monomers and monomer-monomer interaction establishes activating the activation loop in a kinase domain, that activates the further process of transphosphorylation of the specific tyrosine kinases in the kinase domain of ErbB's intracellular part. (wikipedia.org)
ErbB2 has no known binding ligand and absent of an active kinase domain in ErbB3 make this duo preferable to form heterodimers & share each other's active domains to activate transphosphorylation of the tyrosine kinases. (wikipedia.org)
Activation of the tyrosine kinase domain leads to the activation of the whole range of downstream signaling pathways like PLCγ, ERK 1/2, p38 MAPK, PI3-K/Akt and more with the cell. (wikipedia.org)
Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. (nih.gov)
This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m 6 A processing. (molcells.org)
Active mTORC1 phosphorylates the eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and 40S ribosomal protein S6 kinase 1 (S6K1) to promote protein synthesis [ 3 , 4 ]. (springer.com)
Conversely, during starvation mTORC1 is inhibited and autophagy is induced by AMP-activated protein kinase (AMPK), leading to generation of intracellular nutrients and energy during degradation of non-functional or non-essential organelles or protein aggregates [ 4 , 6 ], in turn contributing to cell survival. (springer.com)
Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
Extracellular signal-regulated kinase (ERK) is a serine/threonine protein kinase that functions as the major effector of the Ras protein, a small GTPase. (proteinkinase.biz)
1996) "A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1" Mol Cell Biol. (proteinkinase.biz)
their downstream protein kinase effectors. (sciencepop.org)
For example RAC and CDC42 share two protein serine-threonine kinase effectors in common - PAK and MLK - and inhibitors for both these kinases have been developed. (sciencepop.org)
CDC42 also has distinct kinase effectors such as MRCK and the tyrosine kinase ACK and these kinases too might provide suitable drug targets in cancer. (sciencepop.org)
Activated CDC42 kinase (ACK or TNK2) is a ubiquitously expressed non-receptor tyrosine kinase that binds to and is activated by CDC42 (22). (sciencepop.org)
Some of these proteins, such as MEK, belong to the MAP-Kinase pathway and are critical regulators of cell proliferation and survival. (broadinstitute.org)
The key components of the Igf 1 receptor signaling pathway include the IGF-1 receptor, insulin receptor substrate proteins (IRS), phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). (ebiwinner.com)
One key insight into the Igf 1 receptor signaling pathway is the involvement of phosphoinositide 3-kinase (PI3K) and Akt. (ebiwinner.com)
Akt activation leads to the phosphorylation and inactivation of various downstream targets, including glycogen synthase kinase 3 (GSK3), which regulates glycogen synthesis, and the mammalian target of rapamycin (mTOR), which controls protein synthesis and cell growth. (ebiwinner.com)
We focus on six 'core' effectors that operate in almost all these species - members of the Pak, WASP/WAVE, formin, lipid-kinase, IQGAP and NADPH oxidase families. (biomedcentral.com)
In addition, they play important roles in gene transcription (via activation of mitogen activated protein (MAP) kinase pathways and, in higher eukaryotes, the transcription factor NFκB), generation of reactive oxygen species, apoptosis, and cell-cycle progression. (biomedcentral.com)
Activated Cdc42-associated kinase 1 (Ack1, E.C. 2.7.10.2), also known as TNK2, is a 114 kDa member of the Ack family of mammalian non-receptor tyrosine kinases (NRTKs) which is activated by multiple receptor tyrosine kinases (RTKs) to perform various roles within the cell. (tocris.com)
It was first identified as an inhibitor of the GTPase activity of GTP-bound Cdc42, but it also promotes cell survival via the phosphorylation of several effector proteins, such as the androgen receptor (AR) and protein kinase B (Akt) . (tocris.com)
In addition to a catalytic kinase domain, Ack1 contains seven other domains, which are important for substrate recognition, regulation of enzymatic activity, cellular localization and protein-protein interactions. (tocris.com)
Serine/threonine-protein kinase involved in autophagy in response to starvation. (nih.gov)
They also activate other kinase cascades. (embl-heidelberg.de)
In human cells, SMG1 forms a complex with two NMD effectors SMG8 and SMG9, which inhibit the kinase activity of SMG1 in vitro. (nature.com)
Ras-GTPases act as molecular switches that bind to downstream effectors, such as the protein kinase c-Raf , and localizes them to the membrane resulting in their activation. (bionity.com)
A common feature of these genes is that their products have all been strongly implicated as positive regulators of the Ras/ MAP kinase signal transduction pathway. (bionity.com)
Evidence suggests that nerve growth factor (NGF) induces neurite outgrowth from PC12 cells by activating the receptor tyrosine kinase, TrkA. (biomedcentral.com)
NGF is a neurotrophic factor critical for the survival and maintenance of sympathetic and sensory neurons, and it binds to the high-affinity tyrosine kinase receptor, TrkA, leading to its phosphorylation and the subsequent activation of PI3K/Akt/GSK3β pathways. (biomedcentral.com)
A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation. (stanford.edu)
Activating mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) cause Parkinson's disease and previously we showed that activated LRRK2 phosphorylates a subset of Rab GTPases (Steger et al. (stanford.edu)
These guanosine triphosphatases bind GTP causing the activation of mitogen activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K) and Ras-like (RAL) pathways [ 1 ]. (biomedcentral.com)
Par3 and Par6 bind one another and atypical protein kinase C (aPKC). (rupress.org)

Ras proteins are the founding members of the Ras superfamily of GTPases, which in humans is composed of more than 150 members [ 1 ] [ 2 ] . (encyclopedia.pub)
Ras proteins are membrane-bound small GTPases that act as molecular transducers, coupling cell surface receptors to intracellular effector pathways to regulate cellular processes such as cell proliferation, differentiation, migration, and apoptosis [ 3 ] [ 4 ] . (encyclopedia.pub)
2007), Evolution of the Rho family of ras-like GTPases. (xenbase.org)
Human RAS superfamily proteins and related GTPases. (xenbase.org)
RHO GTPases members of the RAS superfamily of small GTPases are adhesion and growth-factor activated molecular switches that play important roles in tumor development and progression. (sciencepop.org)
Background The RHO family proteins RAC1 CDC42 and RHOA are small GTP-binding proteins that act as molecular switches shifting between an inactive GDP-bound form and an active GTP-bound form that define functions of RHO GTPases. (sciencepop.org)
Upon activation GTP-bound RHO-GTPases interact with a wide spectrum of effectors to regulate various cellular pathways including cytoskeletal dynamics motility cytokinesis cell growth apoptosis and transcriptional activity. (sciencepop.org)
The three best studied members of the RHO family - RAC1 CDC42 and RHOA - are essential for transformation by activated RAS (3 4 and in the case of RAC1 and RAC2 themselves can be oncogenic drivers in human malignancies (5 6 As with RAS the RHO GTPases have proven difficult to Olmesartan medoxomil target directly with small molecule inhibitors. (sciencepop.org)
Although dozens of proteins act downstream of these GTPases, a comparison of effector proteins from evolutionarily diverse organisms suggests that six groups of proteins serve as the core machinery for signaling from Cdc42 and Rac. (biomedcentral.com)
In an effort to understand the fundamental signaling elements, or 'core machinery', required for the function of these GTPases, we describe here the conservation and functional similarities of Cdc42 and Rac effectors in five different species: plant, yeast, fruit fly, roundworm and human. (biomedcentral.com)
Rho GTPases are small (20-30 kDa) GTP-binding proteins of the Ras superfamily. (biomedcentral.com)
Interestingly, small GTPases related to Rac are found even in organisms that lack Ras, such as plants. (biomedcentral.com)
This broad distribution across widely divergent eukaryotic species suggests that Cdc42 and Rac GTPases have an ancient origin, perhaps even predating that of their cousin Ras. (biomedcentral.com)
Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes. (cancerindex.org)
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. (umbc.edu)
The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. (umbc.edu)
GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. (umbc.edu)
Members of your Ras superfamily of little GTPases are widely deemed to be monomeric (23). (calcium-channel.com)
On the other hand, a number of members across the Ras GTPase subfamilies are now identified to dimerize (248), plus a class of tiny GTPases that use dimerization rather than GTPase activating proteins (GAPs) for GTPase activity has been identified (29). (calcium-channel.com)
GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. (embl-heidelberg.de)
Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. (embl-heidelberg.de)
In cell signalling , Son of Sevenless , or SOS , is a gene encoding a guanine nucleotide exchange factor that acts on Ras - GTPases . (bionity.com)
Ras-GTPases are considered inactive when bound to guanosine diphosphate (GDP) and active when bond to guanosine triphosphate (GTP). (bionity.com)
As the name implies, Ras-GTPases possess intrinsic enzymatic activity that converts GTP to GDP plus phosphate. (bionity.com)
SOS (and other guanine nucleotide exchange factors) act by binding Ras-GTPases and forcing them to release of their bound nucleotide (usually GDP). (bionity.com)
Biochemically, these mutations have been shown to similarly effect aberrant activation of the catalytic domain towards Ras-GTPases. (bionity.com)
Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. (biomedcentral.com)
A structural feature that distinguishes the Rho proteins from other small GTPases is the so-called Rho insert domain located between a β strand and an α helix within the small GTPase domain [ 1 - 3 ]. (biomedcentral.com)
Rho GTPases are key integrating molecules from different extracellular signals, as they can be activated by different GEFs. (biomedcentral.com)
In turn, GTP-bound active GTPases can interact with a plethora of different effectors which mediate the different cellular functions of this family of proteins. (biomedcentral.com)
Two factors concur to determine specific Rho GTPase function: tissue specificity of GTPase effectors and distinct intracellular localizations of closely related Rho GTPases, due to different lipid modifications [ 1 ]. (biomedcentral.com)

The GTPase superfamily: conserved structure and molecular mechanism. (xenbase.org)
Like other members of the RAS superfamily, ARF family proteins can be activated by guanine-nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) [ 9 ]. (biomedcentral.com)
Rho proteins belong to the Ras superfamily. (biomedcentral.com)

Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)
Additionally, Ras proteins are recognized as major oncogenes, as mutations in all three Ras genes occur in approximately 30% of human cancers [ 10 ] . (encyclopedia.pub)
29% of melanomas are driven by mutations in N-Ras, while H-Ras mutations appears mutated in 5% of head and neck squamous cell carcinoma and 6% of bladder cancers [ 11 ] . (encyclopedia.pub)
KRAS is one of the most highly mutated proteins in cancer accounting for nearly 30% of cancer related mutations, and 86% of all RAS related mutations (reviewed in (1, 2)) . (cytoskeleton.com)
Mutations to codon 12 in KRAS maintains kRAS in an active, GTP-bound state through preventing GTPase-activating proteins (GAP) association. (cytoskeleton.com)
Mutations that produce abnormally active Ras proteins are common in human cancers, particularly those of the pancreas, lung, and colon. (cshlpress.com)
The contributors review the biochemical characteristics of the different Ras isoforms (HRAS, KRAS, and NRAS), their main effectors and signaling pathways, and the mutations that lead to their constitutive activation. (cshlpress.com)
Mutations of the NF1 gene potentially results in the activation of multiple Ras proteins, which are key regulators of many biologic effects. (biomedcentral.com)
In addition to bronchial tumors, our team is also interested in the characterization of NF1 mutations and more broadly of negative regulators of the RAS-MAPK pathway in pediatric acute lymphoblastic B leukemia (ALL-B). The activation of the main effectors of the pathway is well described but the alterations of the regulators are still poorly understood. (institutcochin.fr)
Scope includes mutations and abnormal protein expression. (cancerindex.org)
sec5 mutations have been identified and characterized in Drosophila in order to delineate the role of the protein in neurons and particularly at synapses. (sdbonline.org)
Soluble Ras doesn't activate Raf SignificanceRas is usually a key signaling molecule in living cells, and mutations in Ras are involved in 30 of human cancers. (calcium-channel.com)
Activating mutations in Ras genes are found in 33% of human cancers, with Ras well recognized as the most commonly mutated oncogene in human cancer. (aacrjournals.org)
Mutations in Ras associated with cancer promote cellular activation by populating the active state of Ras, most frequently by impairing the action of proteins that downregulate its activity. (aacrjournals.org)
In this way these mutations are thought to create SOS1 alleles encoding hyper-activated and dysregulated variants of the protein. (bionity.com)

Notably, the ErbB1 and ErbB4 are the two most studied and intact among the family of ErbB proteins, Which forms functional intracellular tyrosine kinases. (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)
In this review, we summarized the current knowledge of hemocyte-mediated phagocytosis, in particular focusing on the related receptors for recognition and internalization of pathogens as well as the downstream signal pathways and intracellular regulators involved in the process of hemocyte phagocytosis. (frontiersin.org)
2 , 3 A key feature of apoptosis has been defined as the maintenance of an intact cellular membrane (detectable as exclusion of impermeable dyes such as propidium iodide, PI) throughout the apoptotic program to prevent intracellular protein release and subsequent immunological activation. (nature.com)

These findings give a comprehensive view of the evolutionary canvas of the Rho family and provide guides for future structure and evolution studies of other components of Rho signaling pathways, in particular regulators of the RhoGEF family. (xenbase.org)
Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
Our project is to characterize (1) the transcriptome variations of a panel of negative regulators of the pathway, using a targeted transcriptomic study, and (2) the genetic alterations of these effectors in a large cohort of pediatric B-ALLs (including matched relapse samples), using a targeted NGS sequencing study. (institutcochin.fr)
Ras proteins are critical regulators of multiple pathways involved in cellular growth control. (aacrjournals.org)
Therefore, we exposed the MAGIs are crucial regulators of Par polarity proteins that are central towards the rules of pressure distribution in epithelial cells homeostasis. (aboutsciencenow.info)

Reduced SMO-dependent expression of Gli1 was demonstrated in both Tsc1 −/− and Tsc2 −/− cells, and we found that Tsc1 is required for TGF-β induced phosphorylation of SMAD2/3 and subsequent expression of the HH signaling effector and transcription factor GLI2. (springer.com)
During starvation AMPK promotes autophagy by activating ULK1 via phosphorylation at Ser317, Ser555, and Ser777, whereas in the presence of nutrients mTORC1 suppresses autophagy by hampering interaction between AMPK and ULK1 through phosphorylation of ULK1 at Ser757 [ 7 ]. (springer.com)
In this study we used phosphorylation of the transcription factor cAMP response element-binding protein as a functional readout to identify cells responding to EGF and FGF-2. (beauty104.com.tw)
PIP3 then recruits Akt to the plasma membrane, where it is activated by phosphorylation. (ebiwinner.com)
Paxillin, an integrin-assembly protein, has four major tyrosine phosphorylation sites, and the phosphorylation of Tyr31 and Tyr118 correlates with cell adhesion and migration. (silverchair.com)
Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. (nih.gov)
2017). Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation. (stanford.edu)

The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. (wikipedia.org)
Ras signaling is activated by cellular receptors including receptor tyrosine kinases (RTKs), G-protein coupled receptors (GPCRs), cytokines receptors, and extracellular matrix receptors [ 12 ] . (encyclopedia.pub)
Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family. (embl.de)
Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. (embl.de)
The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. (aging-us.com)
The substrate specificities of the ERK1 and ERK2 protein kinases are very similar. (proteinkinase.biz)
Gonzalez FA, Raden DL, Davis RJ (1991) "Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases" J. Biol. (proteinkinase.biz)
Among these effectors are several protein kinases that either are or might be amenable to small molecule inhibition. (sciencepop.org)
RHO-A has a distinct set of effector kinases including the ROCK CITRON Olmesartan medoxomil and PRK1 all of which regulate cellular processes that contribute to tumorigenesis invasion and metastasis (12). (sciencepop.org)
p21 activated kinases (PAKs) the most extensively studied CDC42 and RAC effector proteins consist of two subgroups made up of three members each: group I (PAK1-3) and group II (PAK4-6). (sciencepop.org)
Another common effector of CDC42 and RAC the mixed-lineage kinases (MLKs) are a family of serine/threonine kinases that translate signals from cell surface receptors to MAPKs. (sciencepop.org)
This motif is found in Cdc42/Rac-associated proteins such as the protein kinases Pak, MRCK and Ack, the adaptor proteins Spec and WASP, and, in degenerate form, in the kinases MLK, Mekk4, adaptor Par6, scaffold protein IRSp53, and the Borg proteins. (biomedcentral.com)
Transition of the preRC to an active initiation complex is regulated by cyclin-dependent kinases and other signaling molecules, which promote further protein assembly and activate the mini chromosome maintenance helicase. (usc.edu)
Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)

The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. (embl-heidelberg.de)
Downstream signalling is controlled by both RAS-intrinsic GTP hydrolysis, guanine nucleotide exchange factors (GEFs) that catalyse hydrolysis and GTPase-activating proteins (GAPs) [ 2 ]. (biomedcentral.com)

When ARF family proteins are activated, they bind to effector molecules, which in turn mediate downstream functions. (biomedcentral.com)
Recent work showing that some Ras oncoproteins may be effectively inhibited by small molecules is covered, as is work on alternative targets (e.g., enzymes that catalyze posttranslational modifications of Ras) and inhibitors (e.g., nucleic acids). (cshlpress.com)
There have been limited successes with molecules that disrupt the binding of guanine nucleotide exchange factors to RAC and CDC42 (7-10) as well as with molecules that disrupt GTPase membrane association (11). (sciencepop.org)
The Igf 1 receptor signaling pathway regulates cell growth and survival by activating downstream signaling molecules that promote cell proliferation, inhibit apoptosis, and stimulate protein synthesis. (ebiwinner.com)
Potential therapeutic targets in the Igf 1 receptor signaling pathway include the IGF-1 receptor itself, as well as downstream signaling molecules such as PI3K, AKT, and mTOR. (ebiwinner.com)
In this function, we use a series of quantitative physical methods to map out the tendency of two Ras molecules to bind with each other to type a dimer on membrane surfaces. (calcium-channel.com)
They are small (21-25 kDa) molecules that share structural homology and become activated only when bound to GTP. (biomedcentral.com)
In doing so, this GEF-facilitated exchange of GDP for GTP is associated with structural changes in the GTP-binding protein which influence the degree to which the GTP-binding protein can interact with other molecules. (justia.com)
When GTP is bound, for instance, Ras proteins can interact with effectors and other molecules to affect cell proliferation, differentiation and apoptosis. (justia.com)

In this review, we will focus on how the signal transduction pathways, which play key roles in diverse physiological and pathological conditions, coordinate cellular processes through m 6 A. Given that m 6 A also controls signaling pathways through RNA modification or acting as a ligand, understanding the crosstalk between signal transduction networks and m 6 A RNA processing will provide us insights into the complex biological systems. (molcells.org)
Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
Dr Tabancay's current research interests lie in the fields of pharmacy education, signal transduction pathways leading to cancer, DNA replication, and the use of model organisms to study human diseases. (usc.edu)

Among other members, we will focus our attention on the Rac and Rho subfamilies, as they are the main effectors of cell motility. (biomedcentral.com)

Conversely, m 6 A can modulate the activity of signal transduction networks via m 6 A modification of signaling pathway genes or by acting as a ligand for receptors. (molcells.org)
In humans, three Ras genes ( H-ras , N-ras, and K-ras ) encode four distinct Ras proteins: H-Ras, N-Ras, K-Ras4A, and K-RasS4B, the latter 2 resulting from alternative RNA splicing of the K-ras gen. (encyclopedia.pub)
This domain occurred 39 times on human genes ( 74 proteins). (umbc.edu)
Gain-of-function variants in the three RAS genes have been found in 27 % of human cancers [ 3 ]. (biomedcentral.com)
The degree of activation and the underlying biochemical mechanism differs between variants in the three RAS genes, with the KRAS isoform being the most commonly disrupted in human carcinomas [ 6 ]. (biomedcentral.com)
The GTPase Cdc42 was among the original genes identified with roles in cell polarity, and interest in its cellular roles from yeast to humans remains high. (rupress.org)

In mammalian cells, as many as twenty types of protein have been reported to bind to activated Cdc42 [ 2 ]. (biomedcentral.com)
Freely available on the internet by way of the PNAS open access option.1In mammalian signal transduction, Ras functions as a binary switch in fundamental processes like proliferation, differentiation, and survival (1). (calcium-channel.com)
Part of regulatory feedback loops in autophagy: acts both as a downstream effector and a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. (nih.gov)

The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. (aging-us.com)
Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers the recent progress that has been made in understanding Ras biology, how Ras activation leads to tumorigenesis, and ways in which oncogenic Ras signaling may be targeted therapeutically. (cshlpress.com)
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)
RASSF1A Deficiency Enhances RAS-Driven Lung Tumorigenesis. (cancerindex.org)
It has recently been shown that K-Ras monoubiquitination, upregulates its activity by populating the active GTP-bound state, enhances interactions with certain downstream effectors and promotes Ras-mediated tumorigenesis [1]. (aacrjournals.org)

The normal rate of Ras catalytic GTPase (GTP hydrolysis) activity can be increased by proteins of the RasGAP family, which bind to Ras and increase its catalytic rate by a factor of one thousand - in effect, increasing the rate at which Ras is inactivated. (bionity.com)

Ras-driven cancers are usually aggressive and difficult to treat. (encyclopedia.pub)
Ras GTPase is frequently mutated in different types of cancers that correlate with a poor prognosis [ 11 - 15 ]. (aging-us.com)
These cancers can be difficult to treat because Ras oncoproteins have long been considered undruggable. (cshlpress.com)
This volume is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists concerned with understanding and treating Ras-driven cancers. (cshlpress.com)
We used data generated from genome-scale CRISPR-Cas9 Project Achilles screens to discover vulnerabilities in KRAS-mutant cancer cell lines, and identified the Rho GTPase RAC1 as a key signaling node supporting proliferation and survival of KRAS-mutant cancers. (broadinstitute.org)

Mutant K-RAS has been shown to have both tumor-promoting and -suppressing functions, and growing evidence suggests that the RASSF family of tumor suppressors can act as RAS apoptosis and senescence effectors. (cancerindex.org)
This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. (biomedcentral.com)
We now show that during early apoptosis limited membrane permeabilization occurs in blebs and apoptotic bodies, which allows release of proteins that may affect the proximal microenvironment before the catastrophic loss of membrane integrity during secondary necrosis. (nature.com)
Blebbing, apoptotic body formation and protein release during early apoptosis are dependent on ROCK and myosin ATPase activity to drive actomyosin contraction. (nature.com)

m 6 A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. (molcells.org)
Primary cilia are sensory organelles that coordinate multiple cellular signaling pathways, including Hedgehog (HH), Wingless/Int (WNT) and Transforming Growth Factor-β (TGF-β) signaling. (springer.com)
Ras proteins are essential mediators of a multitude of cellular processes, and its deregulation is frequently associated with cancer appearance, progression, and metastasis. (encyclopedia.pub)
We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras -transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition. (aging-us.com)
Mass spectrometry-based phosphoproteomics identified thirteen protein networks distinctly regulated by DN R-Ras, including multiple networks regulating cellular movement and morphology. (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)
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)
The Igf 1 receptor signaling pathway is a cellular signaling pathway that is activated by the binding of insulin-like growth factor 1 (IGF-1) to its receptor on the cell surface. (ebiwinner.com)
Genetic changes and epigenetic modifications in cancer cells alter the regulation of cellular metabolic pathways providing potential cancer therapeutic targets. (tocris.com)
The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. (mechanobio.info)
Dying cells have been defined as apoptotic by distinguishing features, including cell contraction, nuclear fragmentation, blebbing, apoptotic body formation and maintenance of intact cellular membranes to prevent massive protein release and consequent inflammation. (nature.com)

The Rap2 subgroup is part of the Rap subfamily of the Ras family. (nih.gov)
Neurofibromin loss potentially hyperactivates classic Ras (H-Ras, N-Ras, K-Ras), M-Ras, and R-Ras (R-Ras, R-Ras2/TC21) subfamily proteins. (biomedcentral.com)
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)
All NSP proteins contain an NH 2 -terminal SH2 (Src homology domain 2) domain, a central proline/serine-rich domain, and a COOH-terminal domain with modest homology to Ras subfamily GDP-exchange factors (GEFs). (molvis.org)

In tumors, RAC1 is usually hyper-activated and RAC1 inhibitors such as EHop-016 aim at blocking the interaction of RAC1 with several of its known guanine nucleotide exchange factors (GEFs). (broadinstitute.org)
Guanine nucleotide exchange factors ("GEFs") stimulate the dissociation of the GTP hydrolytic product, GDP, from small GTP-binding proteins, to promote the binding of a new GTP molecule. (justia.com)

Mutant Ras is a driver both in tumor initiation and tumor maintenance [ 5 ] [ 7 ] . (encyclopedia.pub)
The GSEA suggested that ARL9 may be able to upregulate cell adhesion, extracellular matrix receptor interactions, tumor-associated pathways, and downregulate the citrate cycle and tricarboxylic acid cycle pathway, which are involved in the development of colon adenocarcinoma. (biomedcentral.com)
This can provide Ras-expressing tumor cells additional selective advantages under stress or damage. (aging-us.com)
Loss of the Ras GTPase-activating protein neurofibromin promotes nervous system tumor pathogenesis in patients with neurofibromatosis type 1 (NF1). (biomedcentral.com)
We have shown that classic Ras proteins promote proliferation and survival, but not migration, in malignant peripheral nerve sheath tumor (MPNST) cells. (biomedcentral.com)
NF1 is a major tumor suppressor gene encoding neurofibromin, a RAS-GAP (GTPase activating protein) that acts as an inhibitor of the RAS-MAPK pathway by allowing RAS proteins to return to inactive confirmation. (institutcochin.fr)
It has been hypothesized that inactivation of the RASSF1A tumor suppressor facilitates K-RAS-mediated transformation by uncoupling it from apoptotic pathways such as the Hippo pathway. (cancerindex.org)

Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. (xenbase.org)
By regulating filamentous actin, Cdc42 and Rac exert a profound effect on cell shape, polarity, migration, cell:cell and cell:matrix adhesion, protein traffic, and cytokinesis. (biomedcentral.com)
and proteins that interact with members of the Arp2/3 complex and hence the actin cytoskeleton (Table 1 ). (biomedcentral.com)
Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation. (embl-heidelberg.de)
A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. (biomedcentral.com)
In its GTP-bound form, Cdc42 binds several effectors that help direct polarized cell growth: repolarizing actin and microtubules, directing polarized exocytosis via this reoriented cytoskeleton and by direct contact with exocytic machinery, and recruiting proteins such as septins that form a boundary restricting the region of cell growth. (rupress.org)

Activation of mTOR-dependent pathways regulates the specification and differentiation of CD4 + T effector cell subsets. (jci.org)
Here, we report that Gβγ, an important component of the GPCR pathway, is critical for NGF-induced neuronal differentiation of PC12 cells. (biomedcentral.com)
Altogether, our results demonstrate that βγ subunit of heterotrimeric G proteins play a critical role in neurite outgrowth and differentiation by interacting with MTs and modulating MT rearrangement. (biomedcentral.com)

Therefore, autophagy is currently considered as a promising target for anticancer therapy that can also be successful in mutant Ras-expressing tumors characterized by chemotherapy resistance due to the protective autophagy. (aging-us.com)
Since the ERK pathway is often up-regulated in human tumors it represents an attractive target for anticancer drugs development. (proteinkinase.biz)
In human lung tumors, combined activation of K-RAS and inactivation of RASSF1A is closely associated with the development of the most aggressive and worst prognosis tumors. (cancerindex.org)

Despite a large number of promising inhibitors for Ras/Raf/MEK/ERK pathway, recent works show that cancer cells often develop an autophagy-dependent resistance to inhibitors of Ras pathway [ 16 ]. (aging-us.com)
This process is usually regulated by guanine nucleotide-exchange factors GTPase-activating proteins and guanine nucleotide-dissociation inhibitors (1). (sciencepop.org)
While efforts continue to develop direct small GTPase inhibitors a PLCG2 promising and more conventional Olmesartan medoxomil therapeutic approach has been to block the activities of RHO GTPase effectors. (sciencepop.org)
The structures also provide a framework for further studies of the NMD pathway and the design of inhibitors for therapeutic applications. (nature.com)
Because we have shown earlier that prenylation and subsequent methylation/demethylation of γ subunits are required for the Gβγ-MTs interaction in vitro , small-molecule inhibitors (L-28 and L-23) targeting prenylated methylated protein methyl esterase (PMPMEase) were tested in the current study. (biomedcentral.com)

The FGFs are heparin -binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans has been shown to be essential for FGF signal transduction. (beauty104.com.tw)
Further NOD1 Formulation modeling showed that the membrane binding region and the canonical switch I and II regions communicate across the protein by means of long-range side-chain interactions (21) in a conformational choice mechanism (22). (calcium-channel.com)
STAT3 Purity & Documentation Whereas these allosteric modes likely contribute to Ras partitioning and reorientation in vivo, direct functional consequences on Ras protein rotein interactions are poorly understood. (calcium-channel.com)
This may be explained because the SOS1 protein adopts an auto-inhibited conformation dependent on multiple domain-to-domain interactions that cooperate to block access of the SOS1 catalytic core to its Ras-GTPase targets [7] . (bionity.com)
Thus, existing techniques and current knowledge have not used nor addressed the interactions of GEF-H1 with other proteins as a means by which cell proliferation can be controlled or the detection and treatment of cancerous, tumorigenic cells and tissues be developed. (justia.com)

Oncogenic Ras induces the constitutive activation of Ras/Raf/MEK/ERK signaling pathway, which, in turn, activates other effector pathways, in particular, PI3K-mTOR signaling [ 17 ]. (aging-us.com)
By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. (embl-heidelberg.de)

Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Complex proteins 1 and 2 (TSC1/2) negatively regulate protein synthesis by inactivating the mTOR complex 1 (mTORC1) at energy limiting states. (springer.com)
How does the Igf 1 receptor signaling pathway regulate cell growth and survival? (ebiwinner.com)
Proteins that regulate vesicle exocytosis cluster at AZs, composing the cytomatrix at the active zone (CAZ). (eneuro.org)
Our results suggest that although Rab3-GEF acts upstream of Rab3 to control Rab3 localization and likely GTP-binding, it also acts downstream to regulate CAZ development, potentially as a Rab3 effector at the synapse. (eneuro.org)
In this scholarly study, we present proof that MAGI proteins, structural the different parts of AJC whose function continued to be unclear, regulate apical constriction of epithelial cells through the Par polarity proteins. (aboutsciencenow.info)
However, the possible connection between these pathways and how they might ultimately converge to regulate the assembly and organization of MTs during neurite outgrowth is not well understood. (biomedcentral.com)
Cdc42 interacts with proteins that regulate endocytosis and exocytosis and mediate traffic between ER and Golgi. (rupress.org)

Due to their ability to activate multiple MAPK pathways MLKs mediate a variety of biological processes. (sciencepop.org)

In general, K-Ras is the most frequently mutated isoform (accounting for 75% of Ras mutation in cancer), followed by N-Ras (17%) and H-Ras (7%) [ 10 ] . (encyclopedia.pub)
Members of the RAS family of oncogenes are the most frequently mutated in human cancer. (broadinstitute.org)

These four Ras isoforms are ubiquitously expressed and are highly similar in primary sequence, structure, and biochemical properties [ 5 ] [ 6 ] . (encyclopedia.pub)
a variety of upstream signaling pathways can activate Ras-GDP to Ras-GTP, which subsequently selects amongst a number of downstream effectors to elicit a varied but distinct biochemical response (2, 3). (calcium-channel.com)
To determine the mechanism by which ubiquitination activates Ras, we conducted NMR, modeling, biochemical and biological studies of monoubiquitinated H-Ras and K-Ras. (aacrjournals.org)
The detection of mechanical signals, and their integration into biochemical pathways, is integral to the cell's ability to sense, measure and respond to its physical surroundings. (mechanobio.info)

Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)

KRAS functions as a molecular switch in growth factor pathways, regulating proliferation by alternating between its active (GTP-bound) vs inactive (GDP-bound) state. (cytoskeleton.com)
As an alternative, current work aims at targeting crucial KRAS downstream effectors. (broadinstitute.org)
Non-malignant somatic KRAS variants underlie a subset of RAS-associated autoimmune leukoproliferative disorders (RALD). (biomedcentral.com)
This case of idiopathic splenomegaly in childhood due to a somatic variant in KRAS expands our understanding of the clinical spectrum of RAS-associated autoimmune leukoproliferative disorder and emphasizes the value of securing a molecular diagnosis in children with unusual early-onset presentations with a suspected monogenic origin. (biomedcentral.com)
The RAS family consists of three proteins all sharing a highly conserved N-terminus region: Harvey RAS (HRAS), Kirsten RAS (KRAS) and neuroblastoma RAS (NRAS). (biomedcentral.com)

Although the recent Food and Drug Administration (FDA) approval of the first Ras G12C inhibitor is an important milestone, only a small percentage of patients will benefit from it. (encyclopedia.pub)

Recently, a drug that targets mutant RAS G12C specifically has shown promising clinical results and is now the first FDA approved RAS-targeting drug for the treatment of NSCLC, read on for a summary of this drugs journey from discovery to approval, and roadblocks that still lie ahead. (cytoskeleton.com)
What are the potential therapeutic targets in the Igf 1 receptor signaling pathway? (ebiwinner.com)
Current research efforts in the field of Igf 1 receptor signaling pathway are focused on understanding the molecular mechanisms underlying its regulation, identifying novel therapeutic targets, and developing strategies to modulate its activity for the treatment of various diseases. (ebiwinner.com)
Isoform-specific posttranslational lipidation targets the key H-, N-, and K-Ras isoforms to diverse subdomains of the plasma membrane (80). (calcium-channel.com)
This poster summarizes the main metabolic pathways in cancer cells and highlights potential targets for cancer therapeutics. (tocris.com)

These ectatic vessels are lined by flat, benign-appearing endothelial cells, similar to the vessels of normal skin, with similar staining characteristics for endothelial antigens, including fibronectin, von Willebrand factor, and collagenous basement membrane proteins. (medscape.com)
Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. (nih.gov)
Such processes require membrane traffic to particular domains of the cell surface, in order to insert proteins at restricted regions of the membrane, to enlarge particular regions of the cell membrane, or to signal asymmetrically to neighboring cells. (sdbonline.org)
Neurons generate their polarity by directing membrane traffic to growing neurites and growth cones, and by sorting proteins differentially between the axon and dendrites. (sdbonline.org)
This protein is required for many aspects of membrane traffic within neurons, including the elaboration of neurites, but the release of neurotransmitter at the synapse is independent of this exocyst component (Murthy, 2003). (sdbonline.org)
Two important pathways were examined in the current study: (1) a basic pathway of exocytosis that brings new proteins to the cell surface and permits the cell to grow, and (2) synaptic transmission, a specialized form of exocytosis, regulated by Ca 2+ entry, in which vesicles already present at synapses fuse with the membrane and recycle locally (Murthy, 2003). (sdbonline.org)
Urements are consistent using a reorientation of Ras with respect to Urements are consistent with a reorientation of Ras with respect towards the membrane upon GTP binding (19, 20). (calcium-channel.com)
For Ras, dimerization could possibly be significant since Raf, that is recruited to the membrane by binding to Ras, calls for dimerization for activation. (calcium-channel.com)
For instance, H-Ras localizes to cholesterol-sensitive membrane domains, whereas K-Ras does not (11). (calcium-channel.com)
A popular C-terminal S-farnesyl moiety operates in concert with a single (N-Ras) or two (H-Ras) palmitoyl groups, or having a standard sequence of six lysines in K-Ras4B (12), to provide the major membrane anchorage. (calcium-channel.com)
These results indicate that limited membrane permeabilization occurs in blebs and apoptotic bodies before secondary necrosis, leading to acute and localized release of immunomodulatory proteins during the early phase of active apoptotic membrane blebbing. (nature.com)
As a small membrane-associated GTPase, Cdc42 is well suited to designate where and when a particular activity should occur ( Etienne-Manneville, 2004 ). (rupress.org)

Both proteins were activated in neurofibromin-null MPNST cells. (biomedcentral.com)
loss of neurofibromin could cause these Ras proteins to become persistently active, leading to the development of cancer. (biomedcentral.com)
Here, we examined the expression, activation and action of R-Ras proteins in MPNST cells that have lost neurofibromin. (biomedcentral.com)

Ras proteins act as molecular switches that cycle between two conformational states: an active GTP-bound state and an inactive GDP-bound state. (encyclopedia.pub)
Ras proteins are key molecular switches in cell signaling pathways that, when activated, trigger cell growth and division. (cshlpress.com)

The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
All members contain the sequence motifs characteristic of all GTP-binding proteins, bind to GDP and GTP with high affinity. (biomedcentral.com)

Once released from SOS, the Ras-GTPase quickly binds fresh guanine nucleotide from the cytosol. (bionity.com)

3. Differences in the regulation of k-ras and h-ras isoforms by monoubiquitination.Baker R, Wilkerson EM, Sumita K, Isom DG, Sasaki AT, Dohlman HG, Campbell SL.J Biol Chem. (aacrjournals.org)

We will also present our recent work on an oncogenic variant prevalent in lung cancer, K-Ras G12C. (aacrjournals.org)
We find that this activating mutation introduces a redox active cysteine that renders Ras G12C sensitive to thiol oxidation. (aacrjournals.org)

His PhD dissertation entitled "Genetic approaches to the study of Rheb GTPase" utilized the model organisms, Saccharomyces cerevisiae and Schizosaccharomyces pombe , to elucidate Rheb's function in arginine uptake and nutrient sensing. (usc.edu)

In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. (nih.gov)
The IGF-1 receptor signaling pathway plays a crucial role in cell growth, proliferation, and survival. (ebiwinner.com)
Learn more about the IGF-1 receptor signaling pathway and its potential as a therapeutic target. (ebiwinner.com)
What are the key components of the Igf 1 receptor signaling pathway? (ebiwinner.com)
Dysregulation of the Igf 1 receptor signaling pathway has been implicated in various diseases, including cancer, diabetes, and neurodegenerative disorders. (ebiwinner.com)
The Igf 1 receptor signaling pathway is regulated by various mechanisms, including ligand availability, receptor expression and activation, as well as negative feedback loops and cross-talk with other signaling pathways. (ebiwinner.com)
The physiological functions of the Igf 1 receptor signaling pathway include regulation of growth and development, metabolism, tissue repair, and immune function. (ebiwinner.com)
What are the current research efforts focused on in the field of Igf 1 receptor signaling pathway? (ebiwinner.com)
Understanding the Igf 1 receptor signaling pathway has important implications for various diseases, including cancer. (ebiwinner.com)
In conclusion, the Igf 1 receptor signaling pathway is a complex and highly regulated pathway that plays a critical role in various biological processes. (ebiwinner.com)

Dysregulation of this pathway has been implicated in the development and progression of several types of cancer. (ebiwinner.com)

The figure below shows the tridimensional structure of the ErbB family proteins, using the pdb files 1NQL (ErbB-1), 1S78 (ErbB-2), 1M6B (ErbB-3) and 2AHX (ErbB-4): The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher-order oligomers upon activation by a subset of potential growth factor ligands. (wikipedia.org)

Targeting RAS directly is difficult because of the absence of known allosteric regulatory sites, as well as the fact that it has picomolar affinity to GTP/GDP (3) . (cytoskeleton.com)

In this article, we focus on the signaling mechanisms of two of these three subgroups, Cdc42 and Rac, as they are often linked in their physiological functions and have several effectors in common. (biomedcentral.com)

This suggests that DNA replication following escape from G1 arrest in drug is more error prone and provides a potential explanation for the DNA damage observed under long-term RAF-MEK-ERK1/2 pathway inhibition. (babraham.ac.uk)
Senescent ERas cells do not develop cytoprotective autophagy upon inhibition of MEK/ERK pathway due to spatial dissociation of lysosomes and autophagosomes in the senescent cells. (aging-us.com)
Consistent with classical Ras inhibition, DN R-Ras and R-Ras2 knockdown inhibited proliferation. (biomedcentral.com)
However, DN R-Ras inhibition impaired migration and invasion but not survival. (biomedcentral.com)
Inhibition of R-Ras action inhibited proliferation, migration and invasion but not survival. (biomedcentral.com)

There are 11 growth factors that activate ErbB receptors. (wikipedia.org)
G protein-coupled receptors (GPCRs) as well as heterotrimeric G proteins are also involved in regulating neurite outgrowth. (biomedcentral.com)

The heterodimeric TSC complex negatively regulates mTORC1 activity via the GTPase activity of TSC2, towards the small G-protein RHEB (Ras homologue enriched in brain) [ 5 ]. (springer.com)
Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth. (xenbase.org)
Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. (xenbase.org)
Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. (eneuro.org)
OMIM: 190,070) encodes one of three small guanosine triphosphatase proteins belonging to the RAS family. (biomedcentral.com)

One of the mechanisms of high basal autophagy activity in cancer Ras-expressing cells might be associated with high PP2A phosphatase activity targeting directly ULK1-Ser757 that could explain apparent contradiction: maintenance of high mTORC1 functions and high autophagic activity simultaneously [ 22 ]. (aging-us.com)
Key insights into this pathway have provided valuable knowledge about its mechanisms and implications in disease. (ebiwinner.com)
We have investigated novel mechanisms of Ras activation by posttranslational modification. (aacrjournals.org)
These findings represent a paradigm shift in our understanding of the role monoubiquitination may play in protein regulation as well as new mechanisms for regulation of Ras activity. (aacrjournals.org)
We find that monoubiquitination of K- and H-Ras occurs at distinct sites, both of which can upregulate Ras activity, but by different mechanisms [2-4]. (aacrjournals.org)
The long term goal of our research is to elucidate the molecular mechanisms by which proteins are targeted to specific and distinct compartments. (stanford.edu)
We will review these mechanisms and describe the state of knowledge about the proteins involved. (usc.edu)

Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)

GTP binding to Ras induces changes in conformation, mainly in two regions named switch I and switch II, that greatly increase the affinity of Ras for its downstream effectors [ 14 ] [ 15 ] . (encyclopedia.pub)

Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1). (embl.de)
This article explores the components and regulation of the pathway, as well as its implications in various diseases such as cancer and diabetes. (ebiwinner.com)
Subsequently, further distinctions in trafficking pathways have been invoked to explain different forms of regulation and fusion at different domains of the cell. (sdbonline.org)

Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. (nih.gov)
These proteins had a high degree of amino acid identity but were determined to be distinct mitogens. (beauty104.com.tw)
Many, but not all, of these effectors contain a conserved 18 amino-acid binding motif that has been termed CRIB (Cdc42-Rac interactive binding), PBD (p21-binding domain) or GBD (GTPase-binding domain) [ 4 ]. (biomedcentral.com)
Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)

Within neurons, multiple pathways are known to transport proteins and transmitters to the cell surface. (sdbonline.org)

A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. (nih.gov)
Cell surface sensors on immune cells that ordinarily recognize pathogen-associated molecular patterns produced by infectious agents may also interact with DAMPs, leading to the activation of signaling pathways resulting in a nonpathogen-induced 'sterile' inflammatory response. (nature.com)

At sites of polar growth, Cdc42 is activated by guanine nucleotide exchange factors. (rupress.org)

In the presence of nutrients, mTORC1 is activated and promotes cell growth, including protein synthesis and energy storage. (springer.com)
Proteins that act both at the cell surface and intracellularly will be discussed in this thesis, with particular emphasis on the fibroblast growth factors. (beauty104.com.tw)
There are many signaling pathways that lead to RHO activation including those initiated by physical stimuli (mechanical stress or cell-cell and cell-substrate adhesion) and chemical factors (growth factors and cytokines) (2). (sciencepop.org)
Additionally, Akt promotes cell survival by inhibiting pro-apoptotic factors and activating anti-apoptotic factors. (ebiwinner.com)
Another distinction that has been drawn contrasts the constitutive and the regulated pathways to distinguish the ongoing transport of protein and lipid to the cell surface from the ability to secrete hormones and transmitters in response to specific stimuli. (sdbonline.org)
It really is becoming progressively extra clear that the spatial arrangement of proteins within a cell, not just their chemical structure, is an critical aspect of their function. (calcium-channel.com)
Herein, we show that mTOR complex 1 (mTORC1) and mTORC2 have distinct roles in the generation of CD8 + T cell effector and memory populations. (jci.org)
Ack1 is activated by growth factor binding and by homodimerization induced by cell adhesion. (tocris.com)
By coupling the adhesion equipment towards the polarity proteins to modify mobile contractility, we suggest that MAGIs play important and central tasks in maintaining stable state intercellular pressure through the entire epithelial cell sheet. (aboutsciencenow.info)
Right here, we propose a molecular system where AJC scaffolding proteins control apical cell contractility by differentially recruiting MAGI-1 and MAGI-3 to apical AZD-3965 junctions. (aboutsciencenow.info)
Results Lack of ZO proteins highly perturbs Par-3 localization and alters apical morphology We previously demonstrated that depletion of ZO proteins in the mouse mammary epithelial cell range, EpH4, delays the forming of the contractile belt-like AJ18, recommending that ZO proteins are necessary for epithelial polarization. (aboutsciencenow.info)
These studies have served to highlight the role of AND-34/BCAR3 and p130Cas in cell adhesion and migration signaling pathways. (molvis.org)
The DNA in the cell is packaged with histone proteins into chromatin. (usc.edu)
We identified 231 proteins released from actomyosin contraction-dependent blebs and apoptotic bodies by adapted SILAC (stable isotope labeling with amino acids in cell culture) combined with mass spectrometry analysis. (nature.com)
Immune cell responses induced by DAMPs may include cytokine and chemokine release to activate inflammatory cells such as neutrophils and macrophages. (nature.com)
183:1129-1143) provide new insights into how Cdc42 and Par proteins work together to modulate cell adhesion and polarity during embryonic morphogenesis by regulating the traffic of key cell junction proteins. (rupress.org)
Par proteins, like Cdc42, play conserved roles in cell polarity in many contexts, from early embryos to epithelial apical-basal polarity ( Goldstein and Macara, 2007 ). (rupress.org)

The analysis of Cdc42 and Rac function in evolutionarily distant organisms is useful as a tool to uncover the basic activities of these proteins. (biomedcentral.com)

Anatomy16

Organisms35

Diseases4

Chemicals and Drugs69

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes37

Technology, Industry, Agriculture2

Information Science3

Kinase37

GTPases31

Superfamily3

Mutations15

Intracellular4

Regulators5

Phosphorylation7

Kinases14

GAPs2

Molecules9

Signal transduc3

Main effectors1

Genes6

Mammalian3

Tumorigenesis5

Hydrolysis1

Cancers5

Apoptosis4

Cellular11

Subfamily4

GEFs2

Tumor7

Actin6

Differentiation3

Tumors3

Inhibitors5

Interactions5

Constitutive activation2

Regulate7

MAPK1

Frequently mutated2

Biochemical4

Putative1

KRAS5

Inhibitor1

Targets5

Membrane12

Neurofibromin3

Molecular switches2

Bind2

Binds1

Isoforms1

G12C2

Saccharomyces1

Signaling Pathway10

Progression1

Family proteins1

Targeting RAS1

Several effectors1

Inhibition5

Receptors2

Small6

Mechanisms7

Cytoskeletal1

Induces1

Regulation3

Amino acid4

Multiple pathways1

Interact2

Nucleotide1

Cell17

CDC42 and RAC1