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

RAS is a founding member of the RAS superfamily of GTPases. (nih.gov)
Rac is a subfamily of the Rho family of GTPases, small (~21 kDa) signaling G proteins (more specifically a GTPase). (wikipedia.org)
The Rho family of GTPases includes Rac, Rho, and Cdc42 small G-protein groups. (wikipedia.org)
In cellular signaling, the monomeric small GTPases (small G proteins) are known to play an important role in diverse molecular processes. (encyclopedia.pub)
RAS family proteins are membrane-associated, small GTPases that have the function of transmitting a multitude of cellular signals [ 7 ] . (encyclopedia.pub)
Moreover, RAS and RAS GTPases are changed in the development and regression of the corpus luteum. (encyclopedia.pub)
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)
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)
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)
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)
2007), Evolution of the Rho family of ras-like GTPases. (xenbase.org)
Originally demonstrated to control the dynamics of the F- actin cytoskeleton , Rho GTPases have been implicated in many basic cellular processes that influence cell proliferation, differentiation, motility, adhesion, survival, or secretion. (xenbase.org)
Human RAS superfamily proteins and related GTPases. (xenbase.org)
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)
GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. (embl.de)
Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. (embl.de)

The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is frequently de-regulated in human cancer. (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)
Our results demonstrate an association between cognitive impairment and a defect in a signalling pathway that depends on a Ras-like GTPase. (embl.de)

Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) accelerate GTP loading and hydrolysis, respectively. (nih.gov)
They play an important role in the recognition of regulatory factors (GEFs and GAPs) and effectors. (nih.gov)
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)
It is regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. (novusbio.com)
The conserved arginine residue probably functions as a catalytic arginine finger analogous to that seen in ras and Rho-GAPs. (embl.de)
A yeast open reading frame sharing homology with the two known yeast Rab GTPase-activating proteins (GAPs), Gyp6p and Gyp7p, was found in a data base search. (embl.de)
The finding that yeast Rab GAPs share homology with proteins in other species, such as Caenorhabditis elegans and human, suggests the existence of a conserved Rab GAP family. (embl.de)
Similar to other small G proteins, the guanine binding state of Rab3 proteins is regulated by guanine nucleotide exchange proteins or factors (GEPs or GEFs) and GTPase activating proteins (GAPs). (pancreapedia.org)
Other proteins-known as GAPs-lead to the inactivation of the Rab protein. (elifesciences.org)
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.de)

Ras also cooperates with Rho and Ras to activate other downstream signaling pathways. (wikipedia.org)
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)
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)
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)
The catabolic processes regulated by mTORC1 control autophagy via a number of effector regulatory pathways [ 18 , 19 ]. (aging-us.com)
The ovarian cycle is a highly orchestrated, and complex developmental process that depends on functional interactions and critical signaling pathways that communicate between the ovarian microenvironment elements, including the oocyte, granulosa cells, theca cells, and surrounding stromal components, including vascular and immune cells [ 3 ] . (encyclopedia.pub)
RAS family proteins mediate extracellular signals, transduced through their receptors, with multiple signaling pathways, and consequently regulate a wide array of cellular processes [ 8 ] . (encyclopedia.pub)
RAS family proteins play a vital role in the modulation of cell survival, proliferation, and differentiation by signaling through a set of molecular pathways [ 10 ] . (encyclopedia.pub)
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)
Due to their ability to activate multiple MAPK pathways MLKs mediate a variety of biological processes. (sciencepop.org)
What pathways are this gene/protein implicaed in? (cancerindex.org)
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)
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)
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)
Within neurons, multiple pathways are known to transport proteins and transmitters to the cell surface. (sdbonline.org)
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)
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)
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)

Just as other G proteins, Rac acts as a molecular switch, remaining inactive while bound to GDP and activated once GEFs remove GDP, permitting GTP to bind. (wikipedia.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)
Proteins called guanine nucleotide exchange factors, or GEFs for short, activate the Rab protein by promoting the release of GDP and the binding of GTP. (elifesciences.org)
The experiments showed that different amino acids in the active site of the Rab protein are involved when the GEFs mediate the release of the GDP during the activation process. (elifesciences.org)
For example, the amino acid glutamine is involved when the Listeria GEF and one of the human GEFs activate the protein, whereas a different amino acid-aspartate-is involved when one of the other human GEFs is responsible for the activation. (elifesciences.org)
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)

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)

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)
The 70 or so members of the Rab subfamily of proteins perform a wide range of important tasks inside cells. (elifesciences.org)
The Rab subfamily of proteins is part of the large Ras superfamily, and all members of this superfamily are activated and inactivated in a similar way, with the binding and unbinding of GDP and GTP taking place at a structure called the G-domain. (elifesciences.org)

These small 21 kDa proteins function as molecular switches to initialize signaling cascades involved in various cellular processes, including gene expression, cell growth, and differentiation. (nih.gov)
RAS protein plays a vital role in the modulation of cell survival, proliferation, and differentiation by molecular pathway signaling. (encyclopedia.pub)
In the ovarian cycle, repeated patterns of specific cellular proliferation, differentiation, and transformation occur that accompany the process of follicular development and the formation and function of the corpus luteum [ 2 ] . (encyclopedia.pub)
Evidence is accumulating that small G proteins are involved in the regulation of cell growth and differentiation. (nii.ac.jp)
The Igf 1 receptor signaling pathway plays a crucial role in various biological processes, including cell growth, differentiation, and survival. (ebiwinner.com)
This process of division and differentiation is subject to regulation at many levels to control cell production. (justia.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)

When ARF family proteins are activated, they bind to effector molecules, which in turn mediate downstream functions. (biomedcentral.com)
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)
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)
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)
Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)
The ~200 amino acid TBC/rab GTPase-activating protein (GAP) domain is well conserved across species and has been found in a wide range of different proteins from plant adhesion molecules to mammalian oncogenes. (embl.de)
To detect segregation of Ras molecules in raft and disordered lipid domains, we measured Forster Resonance Energy Transfer (FRET) between the donor fluorophore, mant, attached to the protein-bound guanine nucleotides, and the acceptor, rhodamine-conjugated lipid, localized to the liquid-disordered domains. (typeset.io)
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)

Cdc42 interacts with proteins that regulate endocytosis and exocytosis and mediate traffic between ER and Golgi. (rupress.org)

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)
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)
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)
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)
Some of these proteins, such as MEK, belong to the MAP-Kinase pathway and are critical regulators of cell proliferation and survival. (broadinstitute.org)
Serine/threonine-protein kinase involved in autophagy in response to starvation. (nih.gov)
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)
The second Rab3 GEF, known as GRAB, interacts with inositol hexakisphosphate kinase and Rab3A and its protein expression is primarily in brain (41). (pancreapedia.org)
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)
They also activate other kinase cascades. (embl.de)
Par3 and Par6 bind one another and atypical protein kinase C (aPKC). (rupress.org)

Publications] Sasaki,T.: 'A mammalian inhibitory GDP/GTP exchange protein(GDI)for smg p25A is active on the yeast SEC4 protein. (nii.ac.jp)
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)
In mammalian cells, as many as twenty types of protein have been reported to bind to activated Cdc42 [ 2 ]. (biomedcentral.com)

Although these factors possess remarkably similar sequence homology, they do not bind FGFRs and are involved in intracellular processes unrelated to the FGFs (Olsen et al. (beauty104.com.tw)
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)

The RAS family proteins act as binary molecular switches that cycle between active guanosine triphosphate (GTP)-bound and inactive guanosine diphosphate (GDP)-bound states [ 9 ] . (encyclopedia.pub)
Those molecular functions of RAS family proteins exhibit an essential role that co-occurs in the repeated pattern of physiological change during the ovarian cycle. (encyclopedia.pub)
Publications] Kaibuchi,K.: 'Molecular cloning and characterization of the stimulatory GDP/GTP exchange protein(GDS)for smg p21s,ras p21ーlike small GTPーbinding proteins. (nii.ac.jp)
Lately, semisynthetic natively lipidated N-Ras was shown to cluster on supported membranes in vitro, inside a manner broadly consistent with molecular mechanics (MM) modeling of dimers (30). (calcium-channel.com)
The GTPase superfamily: conserved structure and molecular mechanism. (xenbase.org)
Together these proteins form a molecular switch that can be turned on and off. (elifesciences.org)
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)
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)
This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). (embl.de)
The most enriched proteins released were the nucleosomal histones, which have previously been identified as damage-associated molecular pattern proteins (DAMPs) that can initiate sterile inflammatory responses. (nature.com)

The small-G-protein family consists of numerous proteins with varying degrees of homology, one of which is a guanosine nucleotide-binding protein (RAS) [ 4 ] . (encyclopedia.pub)
Because of its localization and homology to the yeast protein Sec4, it was believed to play a role in the terminal steps of secretion. (pancreapedia.org)
Ras proteins are represented by three Ras isoforms with a high degree of homology and nearly 90% sequence identity in the N-terminal GTPase domain33. (typeset.io)

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)
Mutations of the NF1 gene potentially results in the activation of multiple Ras proteins, which are key regulators of many biologic effects. (biomedcentral.com)
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)
Scope includes mutations and abnormal protein expression. (cancerindex.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)
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)
She later continued to study MRes in Cell Biology at UCL, during which she investigated how attenuated mutations in the envelope protein of pathogenic simian immunodeficiency virus affect virological synapse formation and envelope sorting during infection, under the supervision of Prof. Mark Marsh and Dr. Scott Lawrence. (portlandpress.com)

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)

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)
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)

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)

As an alternative, current work aims at targeting crucial KRAS downstream effectors. (broadinstitute.org)

The paralog group of RAS proteins is composed of four isoforms (H-RAS, N-RAS, K-RAS4A, and K-RAS4B) that are encoded by three genes, H-RAS , N-RAS , and K-RAS [ 6 ] . (encyclopedia.pub)
Isoform-specific posttranslational lipidation targets the key H-, N-, and K-Ras isoforms to diverse subdomains of the plasma membrane (80). (calcium-channel.com)
Isoforms H and N of Ras GTPase possess a unique ability to switch their lipid domain preference depending on the type of bound guanine nucleotide (GDP or GTP). (typeset.io)

This Rac1 antibody was developed against a synthetic peptide from amino acid region 100-150 as a part of human Rac1 conjugated to blue carrier protein. (novusbio.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)
RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. (umbc.edu)
The present invention relates generally to improved methods and pharmaceutical compositions for mobilizing hematopoietic stem and progenitor cell from bone marrow into peripheral blood by administration of at least one inhibitor of a GTPase, such as Rac1 and/or Rac2 GTPase. (justia.com)

This process is usually regulated by guanine nucleotide-exchange factors GTPase-activating proteins and guanine nucleotide-dissociation inhibitors (1). (sciencepop.org)

how a cell can detect, measure and respond to the rigidity of its substrate and how these processes apply to larger biological systems. (mechanobio.info)
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)

Structural Insights into the Mechanism of Dynamin Superfamily Proteins. (nih.gov)

Ras cooperates with Cdc42 to regulate Elk1 phosphorylation and transcriptional activity of SRF. (wikipedia.org)
Additionally, reproductive hormones regulate RAS activity in the cellular physiological function of ovarian follicles during pre-ovulatory maturation and ovulation. (encyclopedia.pub)
In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. (novusbio.com)
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)

These motifs are responsible for the recognition of the guanine moiety in GTP and GDP, and contain residues that undergo post-translational modifications that underlie new mechanisms of RAS regulation. (nih.gov)
Post-translational modification within the G4 and G5 motifs activates RAS by populating the GTP-bound "ON" state, either through enhancement of intrinsic guanine nucleotide exchange or impairing GAP-mediated down-regulation. (nih.gov)
In its activated state, Rac participates in the regulation of cell movement, through its involvement in structural changes to the actin Cytoskeleton. (wikipedia.org)
Instead, Ran and its associated proteins shift their focus from nuclear transport to the regulation of microtubule dynamics. (silverchair.com)

Signaling specificity is achieved by a combination of conformational plasticity in Ras itself (4, 5) and dynamic manage of Ras spatial organization (six, 7). (calcium-channel.com)
Rab proteins constitute the largest family of Ras-related small G proteins and play a role in regulating the specificity of membrane trafficking (63, 78). (pancreapedia.org)

We have found that the C-terminal systeine residues of smg p21B, rhoA p21, and smg p25A are geranylgeranylated, and that these prenylation are essential for each small G protein to bind to membranes. (nii.ac.jp)
All members contain the sequence motifs characteristic of all GTP-binding proteins, bind to GDP and GTP with high affinity. (biomedcentral.com)
Rab3 GEP is identical to the human DENN/MADD protein and contains a death domain which can bind the TNFR1 (15). (pancreapedia.org)

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)
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)

These accessory proteins play a fundamental role in regulating activities of RAS superfamily small GTPase via a conserved guanine binding (G)-domain, which consists of five G motifs. (nih.gov)
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)
There is a superfamily of ras p21/ras p21-like small GTP-binding proteins (small G proteins) with GTPase activity. (nii.ac.jp)
In this research project, we have investigated the C-terminal structures of small G proteins, purified the regulatory proteins for small G proteins, and made monoclonal antibodies against small G proteins and their regulatory proteins. (nii.ac.jp)
Most of small G proteins have the unique consensus C-terminal motifs containing at least one cysteine residue. (nii.ac.jp)
Small G proteins have two interconvertible forms, GDP-bound inactive and GTP-bound active forms. (nii.ac.jp)
We have purified and characterized several GDP/GTP exchange proteins (GDP dissociation stimulator (GDS) and GDP dissociation inhibitor (GDI)) and GTPase activating Proteins (GAP) for small G proteins. (nii.ac.jp)
Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. (novusbio.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)
Like other small GTP-binding proteins (e.g. (silverchair.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.de)
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.de)
Belongs to the small GTPase superfamily. (lu.se)
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)

PIP3 then recruits Akt to the plasma membrane, where it is activated by phosphorylation. (ebiwinner.com)
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)
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)
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)
Cryo-EM structures reveal multiple stages of bacterial outer membrane protein folding. (nih.gov)
Poxviruses Encode a Reticulon-Like Protein that Promotes Membrane Curvature. (nih.gov)
Many membrane-associated proteins were found to stably integrate in the rafts, which is critical for their biological function. (typeset.io)
This behavior, however, has never been reproduced in vitro in model bilayers with recombinant proteins, and therefore has been attributed to action of other proteins binding Ras at the membrane surface. (typeset.io)
In a cell, many membrane proteins permanently reside in raft membrane domains, which is essential for their function5, 15-19. (typeset.io)
Directed membrane traffic is essential for many developmental processes, including cell growth, cytokinesis and signaling between cells. (sdbonline.org)
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)
Phagocytosis currently is described as an endocytic process that endogenous foreign particles or pathogens larger than 0.5 μm were first recognized by phagocyte surface receptor and then uptaken and engulfed into a plasma-membrane device, known as phagosome, following initiation of a signaling cascade to generate phagolysosome by fusion of phagosome with lysosomes. (frontiersin.org)
membrane-associated when activated. (lu.se)
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)

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)
PAKs have been implicated in a number of Olmesartan medoxomil cellular processes critical for oncogenic transformation including cell proliferation cell survival adhesion and migration and anchorage-independent growth (13). (sciencepop.org)

Recombinant Gyp1p showed GAP activity on Sec4p, increasing both its steady-state rate and single turnover GTPase activity. (embl.de)

Ras GTPase is frequently mutated in different types of cancers that correlate with a poor prognosis [ 11 - 15 ]. (aging-us.com)
Members of the RAS family of oncogenes are the most frequently mutated in human cancer. (broadinstitute.org)

Furthermore, Rab1 switch II glutamine mutants refractory to activation by DrrA can be activated by TRAPP, showing that a single Rab can be activated by more than one mechanistically distinct GDP-release pathway. (elifesciences.org)
These proteins had a high degree of amino acid identity but were determined to be distinct mitogens. (beauty104.com.tw)
Rather, PDAC cells use a distinct and lengthy process of reversible adaptive plasticity centered on the early fast and later slow mitochondrial network dynamics and metabolic adjustment. (biomedcentral.com)

The structure of the Rabs changes upon binding GTP and mutant Rab3 species have been described similar to Ras that are locked into active and inactive configurations (6). (pancreapedia.org)
A Rab protein is always bound to another molecule, which determines whether it is inactive or active. (elifesciences.org)
Binding to a molecule called GDP makes the Rab protein inactive, while binding to GTP makes it active. (elifesciences.org)

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)
Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange and GTP hydrolysis mechanisms. (elifesciences.org)

Together, these proteins comprise an enzymatic cycle by which Ran binds GTP, hydrolyzes it to GDP (due to the activity of Ran-GAP1), releases the GDP (due to RCC1 activity), and rebinds GTP (due to the presence of a relatively high GTP concentration in the cell). (silverchair.com)

Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. (xenbase.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)
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)

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)

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)
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)

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)

RAS family proteins include 23 genes coding for at least 25 proteins that are divided into eight paralog groups based on sequence identity, structure, and function: RAS, RAS-like (RAL), RAS-related protein (R-RAS), RAS-like protein in tissues (RIT), RAS-related protein Rap (RAP), RAS homolog enriched in brain (RHEB), Dexamethasone-induced RAS-related protein (RASD), and GTP-binding protein Di-RAS (DIRAS) [ 5 ] . (encyclopedia.pub)
This domain occurred 39 times on human genes ( 74 proteins). (umbc.edu)
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 this paper, we report the observation of the nucleotide-dependent switch of lipid domain preferences of the semisynthetic lipidated N-Ras in raft lipid vesicles in the absence of other proteins. (typeset.io)

Ras), Ran's GTP hydrolysis activity and guanine nucleotide affinity are modulated by accessory factors. (silverchair.com)

When bound to GTP, Rac is activated. (wikipedia.org)
The conversion from the GDP-bound to GTP-bound form and the reverse conversion are induced by GDP/GTP exchange and GTPase reactions, respectively. (nii.ac.jp)
It is demonstrated that N-Ras preferentially populated raft domains when bound to Mant-GDP, while losing preference for rafts when it was associated with a GTP mimic, mant-GppNHp. (typeset.io)

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

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)

The extensive cross-talk within these groups of GTPase provides a significant impact on the biological responses of the cell, influencing the activity of the cell cycle machinery. (wikipedia.org)
Given that autophagy is initiated upon suppressed mTORC1 activity, a protective autophagy in Ras-transformed cells with a high level of mTORC1 activity appears to be mTORC1-independent [ 20 , 21 ]. (aging-us.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)
This activity is strongly conserved and probably represents a primordial function of these proteins. (biomedcentral.com)
Gyp1p also stimulated the GTPase activity of several other yeast Rab proteins including Ypt1p, Ypt7p, and Ypt51p but showed no GAP activity on Ypt6p and Ypt32p. (embl.de)
Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif. (xenbase.org)

Although the RAS family of proteins was discovered nearly four decades ago there has not been a viable drug therapy developed to effectively blocks mutant RAS dysfunction. (cytoskeleton.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)
Identification of a Sec4p GTPase-activating protein (GAP) as a novel member of a Rab GAP family. (embl.de)
Residues conserved across the rhoGAP family are largely confined to one face of this bundle, which may be an interaction site for target G proteins. (embl.de)

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)

The DNA in the cell is packaged with histone proteins into chromatin. (usc.edu)

Phagocytosis has been considered as an essential defense mechanism of immune response to pathogens among eukaryotes, which are also implicated in diverse physiological processes, including development, apoptotic, tissue repair, and host defense ( 4 ). (frontiersin.org)

RAS is activated by GTP loading and deactivated upon GTP hydrolysis to GDP. (nih.gov)

What does this gene/protein do? (cancerindex.org)
Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
these proteins are also important in regulating gene transcription. (biomedcentral.com)

The abnormal activities of Rac including its hyperactivation, resistance to degradation, and abnormal localization of its signaling protein components were found to facilitate the development of cancerous cells and resist to anticancer treatment. (wikipedia.org)
m 6 A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. (molcells.org)
A similar increasing trend in the temperature dependence of F/Fo values was observed confirming their conclusion of the localization of the mant-labeled C-terminal N-Ras lipopeptide outside of lipid rafts-readily accessible by acceptor fluorophores. (typeset.io)
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)
A beta-hairpin comprising the nuclear localization sequence sustains the self-associated states of nucleosome assembly protein 1. (colorado.edu)

Thus, we have reviewed the role of RAS protein related to the biological events of the corpus luteum in the ovary. (encyclopedia.pub)
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)

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)
These include four regions participating in guanine nucleotide binding, and effector region corresponding to the effector region in Ras, and a CXC prenylation motif at the C-terminal (45). (pancreapedia.org)

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)

and proteins that interact with members of the Arp2/3 complex and hence the actin cytoskeleton (Table 1 ). (biomedcentral.com)
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)
Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein. (nih.gov)

There are 47093 RhoGAP domains in 46979 proteins in SMART's nrdb database. (embl.de)
Taxonomic distribution of proteins containing RhoGAP domain. (embl.de)
The complete taxonomic breakdown of all proteins with RhoGAP domain is also avaliable . (embl.de)
Click on the protein counts, or double click on taxonomic names to display all proteins containing RhoGAP domain in the selected taxonomic class. (embl.de)
Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. (embl.de)

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)

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)

Anatomy16

Organisms35

Diseases4

Chemicals and Drugs69

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes37

Technology, Industry, Agriculture2

Information Science3

GTPases32

Signalling pathway3

GAPs10

Pathways20

GEFs6

Adaptor proteins1

Subfamily4

Differentiation7

Molecules10

Mediate1

Kinase16

Mammalian3

Intracellular2

Molecular10

Homology3

Mutations8

Kinases7

Apoptosis3

Signal transduction1

Downstream effectors1

Isoforms3

Rac14

Regulated by guanine1

Substrate2

Superfamily Proteins1

Regulate4

Regulation4

Specificity2

Bind3

Several effectors2

Small15

Membrane18

Proliferation5

Recombinant1

Frequently mutated2

Distinct3

Inactive3

Inactivation2

Binds1

Cdc42Hs1

CDC42 and RAC2

Inhibitor1

Phosphorylation2

Differentially1

Genes3

Vesicles1

Hydrolysis activity1

Bound3

Nucleotide exchange1

Tumors1

Activity6

Family4

Inhibitors1

Histone proteins1

Physiological1

Upon GTP hydrolysis1

Gene3

Localization5

Biological2

Motif2

Amino1

Actin cytoskeleton3

RhoGAP5

Subfamilies1

Receptor signali1