Nucleotide exchange ras exchange motif. Medical search. Frequent questions

The protein encoded by this gene is a member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors. (wikipedia.org)
In cell signalling , Son of Sevenless , or SOS , is a gene encoding a guanine nucleotide exchange factor that acts on Ras - GTPases . (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)
Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) accelerate GTP loading and hydrolysis, respectively. (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)
As a proangiogenic response effecter, the interaction of Sema4D with plexin-B1 is dependent on the COOH-terminal PDZ-binding motif of plexin-B1, which binds two guanine nucleotide exchange factors (GEFs) for Rho and is mediated by the activation of Rho-initiated (Ras homolog gene family) pathways ( 4 - 8 ). (jcancer.org)
one binds to phosphorylated tyrosines (the upstream molecule) and the other binds to a proline rich motif, predominately on the guanine nucleotide exchange factor SOS (the downstream molecule) (2). (uvm.edu)
Epac is an acronym for the exchange proteins activated directly by cyclic AMP, a family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). (researchensemble.com)
A Ras exchange motif (REM) domain acts as an intramolecular bridge between the regulatory and the catalytic regions to stabilize the guanine nucleotide exchange (GEF) domain name. (researchensemble.com)
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (embl-heidelberg.de)
The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl-heidelberg.de)
Effectors consist of members from the Tec-family of tyrosine kinases, lipid kinases, phospholipases, and guanine nucleotide exchange elements that additional propagate the sign enabling the activation of multiple pathways, including PI3K/Akt, Ras/ERK, PLC/NFAT, Vav-1/Rac, and IKK/NFB (2, 3). (arcillaresearch.com)
These various functions are controlled through distinct effector proteins and mediated through a GTP-binding/GTPase cycle involving three classes of regulating proteins: GAPs (GTPase-activating proteins), GEFs (guanine nucleotide exchange factors), and GDIs (guanine nucleotide dissociation inhibitors). (umbc.edu)
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)
FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates Cdc42, a member of the Rho (Ras homology) family of the p21 GTPases. (mhmedical.com)
The exchange of GDP to GTP and thus the activation of Rho GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), which act downstream of numerous growth factor receptors, integrins, cytokine receptors, and cadherins. (biomedcentral.com)
The activation process is executed by guanine nucleotide exchange factors, while inactivation is mediated by GTPase-activating proteins (GAPs). (bvsalud.org)
The present invention relates to diagnosing abnormal cell proliferation in biological samples and screening for drugs which inhibit, reduce or abolish cell growth, especially tumorigenic cell growth, by detecting a phosphovariant isoform of a guanine nucleotide exchange factor biomarker, such as the novel GEF-H1S. (justia.com)
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)

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)
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)
Biochemically, these mutations have been shown to similarly effect aberrant activation of the catalytic domain towards Ras-GTPases. (bionity.com)
RAS is a founding member of the RAS superfamily of GTPases. (nih.gov)
A CDC25 homology domain name (CDC25HD) in the C-terminal catalytic domain name exhibits GEF activity for Ras-like GTPases [9]. (researchensemble.com)
Ras homology family (Rho) of small guanosine triphosphatases (GTPases). (umbc.edu)
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)
The class 1A phosphoinositide 3-kinase (PI3K) beta (PI3Kβ) is functionally unique in the ability to integrate signals derived from receptor tyrosine kinases (RTKs), heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs), and Rho-family GTPases. (elifesciences.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)
We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca 2+ /calmodulin (Ca 2+ /CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor-mediated membrane recycling of Rab and Rho GTPases. (rupress.org)
Ral GTPases are activated downstream of Ras and play a crucial role in the development and progression of PDAC. (bvsalud.org)
The small GTPases RalA and RalB are members of the Ras family and activated downstream of Ras. (bvsalud.org)

Thus, upon binding to GTP, the duration of Ras-GTPase activity is limited by the rate at which it hydrolyzes its bound GTP to GDP. (bionity.com)
Once released from SOS, the Ras-GTPase quickly binds fresh guanine nucleotide from the cytosol. (bionity.com)
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)
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)
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)
Two isoforms of Epac, namely Epac 1 (RAPGEF3) and Epac 2 (RAPGEF4), have been identified so far, both of which couple cAMP production to the activation of Rap, a small molecular weight GTPase of the Ras family [11]. (researchensemble.com)
Loss of the Ras GTPase-activating protein neurofibromin promotes nervous system tumor pathogenesis in patients with neurofibromatosis type 1 (NF1). (biomedcentral.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)
The highly conserved Asp-Gln-Arg triad within the GoLoco motif participates directly in GDP binding by extending the arginine side chain into the nucleotide binding pocket, highly reminiscent of the catalytic arginine finger employed in GTPase-activating protein. (embl-heidelberg.de)
A GTPase activator for the nuclear ras-related regulatory protein RAP-1A. (embl-heidelberg.de)
As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. (nature.com)
In the closed conformation, HEAT/ARM core domains shield the GTPase-activating protein-related domain (GRD) so that Ras binding is sterically inhibited. (nature.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)
Ras is a small GTPase that operates as a binary molecular switch between a GDP-bound inactive and GTP-bound active state. (rupress.org)

Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)
Rho proteins belong to the Ras superfamily. (biomedcentral.com)

RAS guanyl releasing protein 4 is a protein in humans that is encoded by the RASGRP4 gene in chromosome 19. (wikipedia.org)
This protein was shown to activate H-Ras in a cation-dependent manner in vitro. (wikipedia.org)
Expression of this protein in myeloid cell lines was found to be correlated with elevated level of activated RAS protein, and the RAS activation can be greatly enhanced by phorbol ester treatment, which suggested a role of this protein in diacylglycerol regulated cell signaling pathways. (wikipedia.org)
Grb2 or growth factor receptor-bound protein 2 is an adaptor protein involved in the Ras signaling pathway. (uvm.edu)
After a ligand binds to the GPCR, it activates a heterotrimeric G-protein, which is composed of three subunits: a guanine nucleotide binding α-subunit, and a βγ-heterodimer (98). (pancreapedia.org)
It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
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)
Mass spectrometry-based phosphoproteomics identified thirteen protein networks distinctly regulated by DN R-Ras, including multiple networks regulating cellular movement and morphology. (biomedcentral.com)
Closer study of an R-Ras regulated pathway containing the signaling protein ROCK1 showed that inhibition of either R-Ras, R-Ras2 or ROCK1 similarly impaired cellular migration and invasion and altered cellular morphology. (biomedcentral.com)
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)
Using EPAC1 (exchange protein directly activated by cAMP 1) as bait in two-hybrid screens of foetal and adult human brain libraries, we identified the LC2 (light chain 2) of MAP1A (microtubule-associated protein 1A) as a protein capable of interaction with EPAC1. (hw.ac.uk)
LC2 was found to interact with a glutathione-S-transferase-fusion protein of the cAMP-binding domain of EPAC1 in a pull-down assay, but not the DEP, REM (Ras exchange motif) or CAT (catalytic) domains. (hw.ac.uk)
The Rasd1 protein is a dexamethasone induced monomeric Ras-like G protein that oscillates in the suprachiasmatic nucleus (SCN). (biomedcentral.com)
DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine-guanosine (CpG) oligonucleotides, a motif often seen in bacterial or viral DNA. (uci.edu)
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)

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)
When GTP is bound, for instance, Ras proteins can interact with effectors and other molecules to affect cell proliferation, differentiation and apoptosis. (justia.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)
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)
The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. (rupress.org)

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

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)

Cyclic nucleotides form when the phosphate group of the molecule of nucleotide triphosphate (ATP or GTP) is attacked by the 3' hydroxyl group of the ribose, forming a cyclic 3',5'-phosphate ester with release of pyrophosphate. (pancreapedia.org)
Furbish AB, Alford AS, Burger P , Peterson YK , Murray-Stewart T, Casero RA, Woster PM . Identification and Characterization of Novel Small-Molecule SMOX Inhibitors. (musc.edu)

FGD1 contains additional motifs commonly associated with signaling proteins, including a pleckstrin homology (PH) domain, an evolutionarily conserved phosphatidylinositol-3-phosphate-binding FYVE domain, and two potential Src-homology 3 (SH3) binding sites. (mhmedical.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)

SHP2 (encoded by PTPN11), SOS1, BRAF, RAF1 and MEK1 positively contribute to RAS-MAPK signaling through complex autoinhibitory mechanisms, that fail when these genes have mutated. (biomedcentral.com)

Since GTP is roughly ten times more abundant than GDP in the cytosol, this usually results in Ras activation. (bionity.com)
SPRED1 recruits Nf1 from the cytosol to the plasma membrane where Ras resides, and Nf1 subsequently can downregulate GTP-bound Ras 14 . (nature.com)
The rationale of this organization may be related to important roles of these proteins as "exchange hubs" for the signaling proteins for their migration from the subcortical cytosol to the membrane. (frontiersin.org)

The targeting motif of Ras is part of the COOH-terminal hypervariable region, which significantly differs amongst the otherwise highly conserved Ras isoforms. (rupress.org)

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)

They also have roles in cell transformation by Ras in cytokinesis, in focal adhesion formation and in the stimulation of stress-activated kinase. (umbc.edu)

All three Ras isoforms have a CAAX sequence at the COOH terminus that specifies farnesylation and further processing of the COOH-terminal cysteine residue. (rupress.org)

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)

In addition to an essential role in regulating cell growth and differentiation, Ras signaling has more recently been linked to a wide range of neuronal functions including synaptic and behavioral plasticity (for review see Thomas and Huganir, 2004 ). (rupress.org)

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

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)

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 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)
Consequently, mutated Nf1 shows altered Ras-GAP activity and leads to uncontrolled signalling in multiple cell signalling pathways. (nature.com)

The presence or absence of 23a regulates Ras/ERK signalling and affects memory and learning behaviour 12 . (nature.com)

Cyclic nucleotides, like other nucleotides, are composed of three functional groups: a ribose sugar, a nitrogenous base, and a single phosphate group. (pancreapedia.org)
A cyclic nucleotide, unlike other nucleotides, has a cyclic bond arrangement between the ribose sugar and the phosphate group. (pancreapedia.org)
There are two main groups of cyclic nucleotides: the canonical or well-established and the non-canonical or unknown-function cyclic nucleotides. (pancreapedia.org)
The two well-established cyclic nucleotides are adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanine-3',5'-cyclic monophosphate (cyclic GMP). (pancreapedia.org)
The non-canonical cyclic nucleotides include the purines inosine-3',5'-cyclic monophosphate (cyclic IMP), xanthosine-3',5'-cyclic monophosphate (cyclic XMP) and the pyrimidines cytidine-3',5'-cyclic monophosphate (cyclic cCMP), uridine-3',5'-cyclic monophosphate (cyclic UMP), and thymidine-3',5'-cyclic monophosphate (cTMP) (145). (pancreapedia.org)
An overview of the non-canonical cyclic nucleotides is provided in Section V. (pancreapedia.org)
A cyclase enzyme (lyase) catalyzes the formation of the cyclic nucleotide from its nucleotide triphosphate precursor ( Figure 1 ). (pancreapedia.org)
This cyclic conformation allows cyclic nucleotides to bind to proteins to which other nucleotides cannot. (pancreapedia.org)
Cyclic nucleotide signaling can be initiated by two general mechanisms. (pancreapedia.org)
The end products of this catalytic reaction are a cyclic nucleotide (cyclic AMP or cyclic GMP) and a pyrophosphate group. (pancreapedia.org)

If its negative charge is not reduced, the nucleotide triphosphate cannot be approached by a nucleophile, which is, in this reaction, the 3' hydroxyl group of the ribose (183). (pancreapedia.org)

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)

Epac proteins also bear a Ras-associating (RA) domain name, which is present in several Ras-interacting proteins. (researchensemble.com)

Most Rho 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. (umbc.edu)
The targeting motif of KRas contains an additional polybasic region adjacent to the CAAX box, whereas HRas and NRas have palmitoylation site(s) instead (Table S1). (rupress.org)

Ras activity relies on proper anchoring to the cytoplasmic leaflet of the plasma membrane (PM) by means of a lipid-based PM targeting motif. (rupress.org)

Pancreatic ductal adenocarcinoma (PDAC), caused by activating mutations in K-Ras, is an aggressive malignancy due to its early invasion and metastasis. (bvsalud.org)

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)

The Switch regions lie within or proximal to the G2 and G3 motifs, and undergo dynamic conformational changes between the GDP-bound "OFF" state and GTP-bound "ON" state. (nih.gov)

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)
Translocation is reversible and mediated by the polybasic-prenyl membrane targeting motif of KRas. (rupress.org)
Such a membrane-anchoring strategy has been adopted by a wide range of signaling proteins ( Fivaz and Meyer, 2003 ) with significant variations in the structure of these motifs (see Table S1). (rupress.org)
Dynein light chain LC8-nNOS from acto-myosin Va is possibly exchanged with shank, which thereafter facilitates transposition of nNOS for binding with palmitoyl-PSD95 at the nerve terminal membrane. (frontiersin.org)

All members contain the sequence motifs characteristic of all GTP-binding proteins, bind to GDP and GTP with high affinity. (biomedcentral.com)

Platelets is involved in the thrombus formation by aggregating each other through association of activated αIIbß3 integrin with the Arg-Gly-Asp (RGD) motif-containing its ligands such as fibrinogen and von Willebrand factor. (bvsalud.org)

Here, we provide a comprehensive review of post-translational modifications in the RAS G4 and G5 motifs, and describe the role of these modifications in RAS activation as well as potential applications for cancer therapy. (nih.gov)
Here, we describe the first transgenic mouse model for activation of K-RAS in the lung in a RASSF1A-defective background. (cancerindex.org)

Zn incubation of Nf1 leads to reduced Ras-GAP activity with both protomers in the self-inhibited, closed conformation stabilized by a Zn binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker. (nature.com)
We conclude that the polybasic-prenyl motif acts as a Ca 2+ /CaM-regulated molecular switch that controls PM concentration of KRas and redistributes its activity to internal sites. (rupress.org)

We have shown that classic Ras proteins promote proliferation and survival, but not migration, in malignant peripheral nerve sheath tumor (MPNST) cells. (biomedcentral.com)

However, it is unclear whether R-Ras, R-Ras2 and M-Ras are expressed and hyperactivated in MPNSTs and, if so, whether they contribute to MPNST pathogenesis. (biomedcentral.com)
Giannella RA (1981) Pathogenesis of acute bacterial diarrheal disorders. (springer.com)

The G4 and G5 motifs are the focus of the present work and lie outside Switch regions. (nih.gov)

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)

It contains a Ras exchange motif, a diacylglycerol-binding domain, and two calcium-binding EF hands. (wikipedia.org)
RBD, Ras-binding domain of Raf-1. (rupress.org)

Anatomy17

Organisms6

Diseases1

Chemicals and Drugs132

Analytical, Diagnostic and Therapeutic Techniques and Equipment30

Phenomena and Processes69

Information Science4

Health Care1

Guanine nucleotide exchange20

GTPases15

GTPase14

Superfamily2

Protein15

Effectors2

Pathway3

Hydrolysis1

Intracellular1

Molecule2

Homology1

Gene1

Genes1

Cytosol3

Highly conserved1

Effector1

Kinase1

Isoforms1

Subfamily1

Differentiation1

Neurofibromin3

Inactivation1

Pathways3

Regulates1

Cyclic10

Triphosphate1

Inactive1

Epac1

CaaX2

Plasma membrane1

Mutations1

Moiety1

Bound1

Membrane4

Sequence1

Ligands1

Activation2

Activity2

Tumor1

Pathogenesis2

Regions1

Absence1

Domain2