Ras gtpase activating proteins membrane associated ras gtpase activating proteins. Medical search. Frequent questions

SPRED1 recruits Nf1 from the cytosol to the plasma membrane where Ras resides, and Nf1 subsequently can downregulate GTP-bound Ras 14 . (nature.com)
This model is supported by the observation that Gap1 appears to be constitutively associated with the plasma membrane (Powe, 1999). (sdbonline.org)
The α 2C -ARs mobilized from the perinuclear region to intracellular filamentous structures and to the plasma membrane. (johnshopkins.edu)
Ras is a GTPase that is anchored to the intracellular side of the plasma membrane through its post-translational lipid modifications. (biolegend.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)
Nevertheless, whether VGCC inhibition is because of interference with route trafficking towards the plasma membrane by RGK protein [21] or RGK-mediated inactivation of stations already at the top [8,16], continues to be questionable. (health-ground.com)
This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. (nih.gov)
In SK-N-SH cells, carbachol induced a rapid and transient translocation of tubulin to the plasma membrane, microtubule reorganization, and a change in cell shape as demonstrated by confocal immunofluorescence microscopy. (jneurosci.org)

This protein binds inositol 1,3,4,5-tetrakisphosphate to stimulate the activity of Ras p21 and negatively regulates the Ras signaling pathway. (wikipedia.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)
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)
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)
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)
Antigen binding to the T cell receptor (TCR) can also lead to Ras signaling through activation of phospholipase C (PLC) and protein kinase C (PKC). (biolegend.com)
We recently showed phosphorylation of Drosophila Plexin A by cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and subsequent inhibition of plexin-mediated repulsive guidance. (stanford.edu)
They also activate other kinase cascades. (embl-heidelberg.de)
Rho2 activates the protein kinase C homolog Pck2, and Pck2 controls Mok1, the major (1-3) alpha-D-glucan synthase. (umbc.edu)
We observed that direct stimulation with LT D4, induced intestinal epithelial cell migration, through activation of the CysLT1 receptor, phosphotidylinositol-3 kinase, Vav2 and Rac localisation to membrane ruffles. (lu.se)
The integrin dependent COX-2 expression was shown to be mediated through the activation of CD47 and its associated G?i3 protein, which in turn lead to protein kinase C? (lu.se)
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)
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 protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. (bioss.com.cn)
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. (bioss.com.cn)
Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. (bioss.com.cn)
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)
Hepatocyte growth factor receptor (c-Met), a member of tyrosine protein kinase receptors (TPKR), is phosphorylated during LPLI-induced proliferation, but tumor necrosis factor alpha (TNF-alpha) receptor has not been affected. (biomedcentral.com)

There is a superfamily of ras p21/ras p21-like small GTP-binding proteins (small G proteins) with GTPase activity. (nii.ac.jp)
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)
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)
Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)
The GTPase superfamily: conserved structure and molecular mechanism. (xenbase.org)
Human RAS superfamily proteins and related GTPases. (xenbase.org)
Belongs to the small gtpase superfamily. (lu.se)
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)
Rho GTPases are small (20-30 kDa) GTP-binding proteins of the Ras superfamily. (biomedcentral.com)

The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1) 1 , 2 . (nature.com)
Increasingly, mutations in genes that encode postsynaptic proteins belonging to the PSD-95 protein complex, continue to be identified in neurodevelopmental disorders (NDDs) such as autism spectrum disorder, intellectual disability and epilepsy. (nih.gov)
Here, by using genetically engineered mice and innovative touchscreen-based cognitive testing, we sought to investigate whether loss-of-function mutations in genes encoding key interactors of the PSD-95 protein complex display shared phenotypes in associative learning, updating of learned associations and reaction times. (nih.gov)
Our genetic dissection of mice with loss-of-function mutations in Syngap1, Nlgn3, Dlgap1, Dlgap2 and Shank2 showed that distinct components of the PSD-95 protein complex differentially regulate learning, cognitive flexibility and reaction times in cognitive processing. (nih.gov)
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)
Des mutations dans le gène SYNGAP1, qui code pour une protéine activatrice GTPase de Ras, sont liées à la déficience intellectuelle chez l'humain. (umontreal.ca)
Numerous studies have linked intellectual disability with mutations in genes coding for protein active at the synapses. (umontreal.ca)
De novo mutations in the SYNGAP1 gene, coding for a GTPase-activating protein, causes moderate to severe intellectual disability. (umontreal.ca)
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)
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)

Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. (embl.de)
Both guanine nucleotide-exchange proteins and GTPase-activating proteins (GAPs) for ARFs have been cloned recently. (embl.de)
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)
The major distinguishing features of the RGK protein family include: calmodulin and 14-3-3 protein binding sites, noncanonical amino acid substitutions in the guanine nucleotide binding domain, and a lack of identified guanine nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs) buy Decitabine [1]. (health-ground.com)
As with other Rho family GTPases, the GDP/GTP cycling is regulated by GEFs (guanine nucleotide exchange factors), GAPs (GTPase-activating proteins) and GDIs (guanine nucleotide dissociation inhibitors). (umbc.edu)

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)
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)
Rem2 is a member of the RGK family of small Ras-like GTPases whose expression and function is regulated by neuronal activity in the brain. (health-ground.com)
Introduction The RGK (Ras, Rem, Rem2, Gem/Kir) protein family is a subclass of small Ras-like GTPases structurally distinct from canonical GTPases. (health-ground.com)
Ras homology family 2 (Rho2) of small guanosine triphosphatases (GTPases). (umbc.edu)
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)
2007), Evolution of the Rho family of ras-like GTPases. (xenbase.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)
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)
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 oncogenic role of TLR4 activated by endotoxin has been confirmed by others in a different liver tumor model 10 . (nature.com)
The NF1 gene product, neurofibromin, is a GTPase-activating protein and acts as a tumor suppressor by negatively regulating the small GTPase, Ras. (bvsalud.org)
Tumor cells are able to disrupt membrane transport regulators, thereby enhancing migration and invasion. (biomedcentral.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)
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)
Mutant Ras is a driver both in tumor initiation and tumor maintenance [ 5 ] [ 7 ] . (encyclopedia.pub)

The postsynaptic terminal of vertebrate excitatory synapses contains a highly conserved multiprotein complex that comprises neurotransmitter receptors, cell-adhesion molecules, scaffold proteins and enzymes, which are essential for brain signalling and plasticity underlying behaviour. (nih.gov)
Ras signaling can be thought of in simple terms as occuring downstream of receptor tyrosine kinases, triggered by association of adaptor proteins with the phosphorylated cytoplasmic tails of these receptors. (sdbonline.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)
Its activity is directed by intracellular signals mediated by various types of receptors such as G protein-coupled receptors. (embl-heidelberg.de)
an enzyme involved in the production of various eicosanoids) expression, by activating integrin collagen receptors. (lu.se)
Ras is associated with growth factor receptors in an inactive GDP-bound state. (ctsqena.com)
It is suggested that G-protein-coupled receptors might modulate cytoskeletal dynamics, intracellular traffic, and cellular architecture. (jneurosci.org)

The presence or absence of 23a regulates Ras/ERK signalling and affects memory and learning behaviour 12 . (nature.com)
In vascular smooth muscle cells derived from human dermal arterioles (micro-VSM), Rap1 selectively regulates expression of G protein-coupled α 2C -adrenoceptors (α 2C -ARs) through JNK-c-jun nuclear signaling. (johnshopkins.edu)
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)
The microtubule protein tubulin regulates adenylyl cyclase and phospholipase Cβ 1 (PLCβ 1 ) signaling via transactivation of the G-protein subunits Gαs, Gαi1, and Gαq. (jneurosci.org)

upon elevation of Ca2+ and IP4 concentrations, the PH domain binds to IP4 thereby stimulating catalytic activity, while at the same time the C2a domain takes over the role of membrane tether. (sdbonline.org)
We had reported that the ARF domain of ARD1 binds specifically GDP and GTP and that the amino-terminal extension acts as a GAP for the ARF domain of ARD1 but not for ARF proteins. (embl.de)
When mutated, p120 Ras GTPase-activating protein binds to Krev-1/rap1a, an integrin β1-mediated cell adhesion and angiogenesis protein. (medscape.com)
EGFR is a cell surface protein that binds to epidermal growth factor. (bioss.com.cn)

Cullen, 1997), suggesting that an increase in intracellular IP4 levels leads to the release of the PH domain from the membrane. (sdbonline.org)
ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins recognized as critical components in intracellular vesicular transport and phospholipase D activation. (embl.de)
Intracellular signaling by the second messenger cyclic AMP (cAMP) activates the Ras-related small GTPase Rap1 through the guanine exchange factor Epac. (johnshopkins.edu)
In human microVSM, increasing intracellular cAMP by direct activation of adenylyl cyclase by forskolin (10 μM) or selectively activating Epac-Rap signaling by the cAMP analog 8-pCPT-2′-O-Me-cAMP (100 μM) activated RhoA, increased α 2C -AR expression, and reorganized the actin cytoskeleton, increasing F-actin. (johnshopkins.edu)
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)
Lipid binding is essential for proper intracellular localization via membrane attachment. (umbc.edu)
Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. (embl-heidelberg.de)
Cytoskeletal proteins appear to be involved in the control of intracellular signaling. (jneurosci.org)

The RASA3 (RAS p21 Protein Activator 3) gene encodes the Ras GTPase activating protein. (wikipedia.org)
R-Ras GAP is a membrane-associated molecule with stronger GAP activity for R-Ras, an activator of integrin, than H-Ras. (elsevierpure.com)

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)

This gene encodes eight alternatively spliced mRNA transcript, which produce five different protein isoforms. (wikipedia.org)
The RASA1 gene encodes p120 Ras GTPase-activating protein. (medscape.com)

One of the quintessential examples having long-range allosteric regulation is the ternary complex, SPRED1-RAS-neurofibromin type 1 (NF1, a RAS GTPase-activating protein), in which SPRED1 facilitates RAS-GTP hydrolysis by interacting with NF1 at a distal, allosteric site from the RAS binding site. (bvsalud.org)
Our findings suggested that SPRED1 loading allosterically enhanced KRAS-NF1 binding, but hindered conformational transformation of the NF1 catalytic center for RAS hydrolysis. (bvsalud.org)
The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs. (embl.de)

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)
GTP-bound Ras activates Raf to trigger a phosphorylation cascade involving mitogen-activated protein kinases (MEKs). (biolegend.com)
Protein phosphorylation is one of the widely used posttranslational modifications that alter protein function in vivo. (stanford.edu)
This phosphorylation occurs in the active site of the plexin GTPase-activating protein (GAP) domain, which in turn inhibits endogenous GAP activity toward Ras/Rap family small GTP-binding proteins by recruiting the phospho-serine/threonine-binding protein 14-3-3ε. (stanford.edu)
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)

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)

This causes adaptor protein GRB2 to recruit SOS, a guanine nucleotide exchange factor, which then facilitates binding of GTP to Ras. (biolegend.com)
The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. (nih.gov)
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)

The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (embl-heidelberg.de)
Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. (xenbase.org)
The contractile ring is made up of structural proteins, including actin filaments and myosin II filaments. (jove.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)
and proteins that interact with members of the Arp2/3 complex and hence the actin cytoskeleton (Table 1 ). (biomedcentral.com)

Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. (embl-heidelberg.de)
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-heidelberg.de)

Consequently, mutated Nf1 shows altered Ras-GAP activity and leads to uncontrolled signalling in multiple cell signalling pathways. (nature.com)
TBC1D15 activated three novel oncogenic pathways to promote self-renewal, p53 loss, and Nanog transcription in TICs. (nature.com)
Ras proteins are key molecular switches in cell signaling pathways that, when activated, trigger cell growth and division. (cshlpress.com)
However, it remains challenging to elucidate dominant allosteric signal transduction pathways, especially for large and multi-component protein machineries where long-range allosteric regulation exits. (bvsalud.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)
Due to their ability to activate multiple MAPK pathways MLKs mediate a variety of biological processes. (sciencepop.org)
an adapter protein coupling the receptor to downstream signaling pathways. (bioss.com.cn)
Activated TPKR could activate its downstream signaling elements, like Ras/Raf/MEK/ERK, PI3K/Akt/eIF4E, PI3K/Akt/eNOS and PLC-gamma/PKC pathways. (biomedcentral.com)

Depending on the different transcript variant that is translated, 5 different possible protein isoforms are encoded by C13orf46. (wikipedia.org)
Other protein isoforms encoded by the C13orf46 gene are similar to either of these two versions of the C13orf46 protein. (wikipedia.org)
These four Ras isoforms are ubiquitously expressed and are highly similar in primary sequence, structure, and biochemical properties [ 5 ] [ 6 ] . (encyclopedia.pub)
Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. (bioss.com.cn)

The NF1-GRD stimulates Ras GTPase activity in turning off signalling. (bvsalud.org)
Activated ERK1/2 also phosphorylates the GTPase dynamin-related protein (Drp1), which then stimulates mitochondrial fission. (cdc.gov)

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)
Thus, a comprehensive understanding of the activation and inactivation of these novel proteins is of utmost interest. (elifesciences.org)

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)
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)
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)
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)

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)
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)

When ARF family proteins are activated, they bind to effector molecules, which in turn mediate downstream functions. (biomedcentral.com)
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)
The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. (bioss.com.cn)

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)

This ultimately results in the translocation of ERK to the nucleus where it phosphorylates and activates a number of transcription factors like Elk1, initiating expression of genes that promote cell survival and growth. (biolegend.com)
Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. (bioss.com.cn)
Cyclins and cyclin-dependent kinases (CDKs) form a complex which phosphorylates proteins that drive the cell through the cell cycle. (ctsqena.com)
For example, the cvclinD/CDK4 complex phosphorylates the retinoblastoma protein, which promotes progression through the G^S checkpoint. (ctsqena.com)

Syngap1 haploinsufficiency increases activity level of Ras-ERK-mTOR, causing excessive insertion of AMPA receptor at the postsynaptic membrane of excitatory neurons and affects spine morphology. (umontreal.ca)
This protein is a receptor for members of the epidermal growth factor family. (bioss.com.cn)
Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. (bioss.com.cn)
Receptor binding causes GDP to be replaced with GTP, activating ras. (ctsqena.com)
These observations presented a spatial and temporal resolution of the sequence of events underlying receptor-evoked involvement of tubulin in G-protein-mediated signaling. (jneurosci.org)

Ras GTPase-activating proteins (GAP) are negative regulators of Ras that convert active Ras-GTP to inactive Ras-GDP. (elsevierpure.com)

The p53 interacting partner protein NUMB (homology of numb protein) preserves this intrinsic cellular asymmetry by preventing ubiquitin-mediated proteolysis of p53 catalyzed by the MDM2 E3 ubiquitin ligase 11 . (nature.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)
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)
The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, oxidative stress, and the accumulation of misfolded proteins. (mdpi.com)

As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. (nature.com)
Association of the proto-oncogene product dbl with G protein betagamma subunits. (embl-heidelberg.de)

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)
The GTPase signalling molecules RhoA and Rac1 regulate merlin function, but to date only mutation in the NF2 gene has been identified as a causal event in schwannoma formation. (bmj.com)
A protein called RhoA is the chief regulator of contractile ring assembly and function. (jove.com)
To ensure the contractile ring is formed in the right place, RhoA is activated locally at the cell cortex, near the equator of the cell. (jove.com)
RhoA activity is transiently inhibited at the initial phase of integrin engagement, when Cdc42- and/or Rac1-mediated membrane spreading and ruffling predominantly occur. (silverchair.com)
We found that mutation of Tyr31/118 caused enhanced activation of RhoA and premature formation of stress fibers with substantial loss of efficient membrane spreading and ruffling in adhesion and migration of NMuMG cells. (silverchair.com)
We conclude that Tyr31/118-phosphorylated paxillin serves as a template for the localized suppression of RhoA activity and is necessary for efficient membrane spreading and ruffling in adhesion and migration of NMuMG cells. (silverchair.com)

TBC1D15-NOTCH1 interaction activated and stabilized NOTCH1 which upregulated transcription of NANOG essential for TIC expansion. (nature.com)

LPLI-induced cell cycle progression can be regulated by the activation or elevated expressions of cell cycle-specific proteins. (biomedcentral.com)

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)
To clarify the physiological role of R-Ras GAP, we generated mice that express mutant Ras GAP with knocked down activity. (elsevierpure.com)
Despite this activity, NF1-GRD has been demonstrated to bind to other different proteins, such as SPRED1 or MC1R. (bvsalud.org)
Classical GAP proteins accelerate GTPase activity by supplying an arginine finger to the active site. (embl.de)
The phosphorylated form of 40S ribosome protein S6 is thus a marker for mTORC1 activity. (springer.com)
In particular, we propose that Arg 85 and Asn 194 are involved in binding G proteins and enhancing GTPase activity. (embl-heidelberg.de)
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. (nih.gov)
The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl-heidelberg.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)
The described setup and experimental design enable real-time monitoring of substrate turnover in light-activated enzymes on a molecular scale, thus opening the pathway to a deeper understanding of enzyme activity and protein-protein interactions. (elifesciences.org)
this is augmented by GTPase activating protein, v. Mutated ras inhibits the activity of GTPase activating protein. (ctsqena.com)
This activity is strongly conserved and probably represents a primordial function of these proteins. (biomedcentral.com)

Evidence is accumulating that small G proteins are involved in the regulation of cell growth and differentiation. (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)

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

An amino-terminal portion conserved among a subset of Dbl family proteins is sufficient for the binding of Gbetagamma. (embl-heidelberg.de)

This biophysical characterization is crucial in deciphering NF1-GRD interactome and in finding biochemical features, modulating possible protein interactions. (bvsalud.org)
This activation leads to effector protein interactions, activation, and biological responses in the vasculature, including vasorelaxation. (johnshopkins.edu)

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)

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)
Importantly compelling genetic and pharmacologic evidence exists that shows that inhibiting group I PAKs can block transformation by oncogenic drivers such as ERBB2 (14) and K-RAS (15). (sciencepop.org)

In this review we will highlight mechanisms that control targeting of PSD-95 at the synapse, and discuss how this molecule influences the retention and clustering of diverse synaptic proteins to regulate synaptic structure and strength. (frontiersin.org)
The mutant proteins often retain some of their capabilities but are no longer sensitive to the controls that regulate the normal form of the protein. (cancerquest.org)
Because most tubulin is not membrane associated, this study investigates whether tubulin translocates to the membrane in response to an agonist so that it might regulate G-protein signaling. (jneurosci.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)
In mammalian cells, as many as twenty types of protein have been reported to bind to activated Cdc42 [ 2 ]. (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)
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)

Fukuda, 1996), implying that release of the PH domain from the membrane is accompanied by activation of the catalytic domain. (sdbonline.org)

Indirect stimulation, by activating COX-2 expression in a ?2?1 integrin dependent manner was able to elicit a migratory response. (lu.se)

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)
RGK proteins have been implicated in mediating cytoskeletal rearrangements [2C5] and inhibition of voltage-gated calcium channel currents [6C10]. (health-ground.com)
Among these effectors are several protein kinases that either are or might be amenable to small molecule inhibition. (sciencepop.org)

Among these regulatory proteins, we have cloned the cDNAs of smg p21 GDS, smg p25A GDI, and rho GDI, and made monoclonal antibodies against them. (nii.ac.jp)

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)

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)

Here, we provide cryoelectron microscopy (cryo-EM) structures that reveal an extended neurofibromin homodimer in two functional states: an auto-inhibited state with occluded Ras-binding site and an asymmetric open state with an exposed Ras-binding site. (bvsalud.org)
Our findings suggest a role for nucleotides in neurofibromin regulation and may lead to therapeutic modulation of Ras signaling. (bvsalud.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)

Publications] Araki,S.: 'Role of the Cーterminal region of smg p25A in its interaction with membranes and the GDP/GTP exchange protein. (nii.ac.jp)
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-heidelberg.de)
Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190. (embl-heidelberg.de)
The interaction of tubulin with these polypeptides involves a GTP transfer from the exchangeable GTP-binding site (E site) of tubulin to Gα, which activates the G-protein (transactivation) ( Roychowdhury and Rasenick, 1994 ). (jneurosci.org)

By establishing a PC12 subclone that stably expresses exogenous R-Ras GAP, it was found that NGF reduced endogenous R-Ras GAP but not exogenous R-Ras GAP, suggesting that down-regulation of R-Ras GAP occurs at the transcription level. (elsevierpure.com)
These results show essential roles of R-Ras GAP in development and differentiation: its expression is needed for embryonic development of blood vessel barriers, whereas its down-regulation facilitates NGF-induced neurite formation of PC12 cells via maintaining activated R-Ras. (elsevierpure.com)
Allosteric regulation is the most direct and efficient way of regulating protein function, wherein proteins transmit the perturbations at one site to another distinct functional site. (bvsalud.org)
Additionally, RGK proteins are differentially expressed in specific tissues with transcriptional regulation of their mRNA manifestation mediated by way of a selection of extrinsic elements (i.e. blood sugar, mitogens, and neuronal depolarization) [1,11C14]. (health-ground.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)
Ras-driven cancers are usually aggressive and difficult to treat. (encyclopedia.pub)

Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth. (xenbase.org)

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)
Recently, the signaling proteins involved in LPLI-induced proliferation merit special attention, some of which are regulated by mitochondrial signaling. (biomedcentral.com)
Recently, a large number of signaling proteins reported play an important key role in the process of LPLI-induced cell proliferation, probably due to the fact that the molecular events they are involved in are the basic response of the cells to extracellular stimuli. (biomedcentral.com)

Ras activated by this mechanism drives the PI3K pathway to initiate expression of cell growth genes. (biolegend.com)
Genes whose protein products stimulate or enhance the division and viability of cells. (cancerquest.org)
Genes whose protein products can directly or indirectly prevent cell division or lead to cell death. (cancerquest.org)
There is no longer a need for signals to activate these genes. (cancerquest.org)
This domain occurred 99 times on human genes ( 174 proteins). (umbc.edu)

1. Bcl2 normally stabilizes the mitochondrial membrane, blocking release of cytochrome c. (ctsqena.com)
2. Mitochondrial membrane is further stabilized, prohibiting apoptosis. (ctsqena.com)

the Ras GTPase and NF?B activation. (lu.se)
COX-2 expression is synonymous with activation of the protein. (lu.se)
After the spectroscopic characterization of the late rhodopsin photoproducts, we analyzed truncated variants and revealed the involvement of the cytosolic N-terminus in the structural rearrangements upon photo-activation of the protein. (elifesciences.org)

Merlin has high homology with the ERM proteins (ezrin, radixin, and moesin) and shares an amino-terminal domain. (bmj.com)

Proteins in cells with or without DN R-Ras expression were differentially labeled with SILAC and mass spectrometry was used to identify phosphoproteins and determine their relative quantities in the presence and absence of DN R-Ras. (biomedcentral.com)

Anatomy46

Organisms9

Diseases1

Chemicals and Drugs121

Analytical, Diagnostic and Therapeutic Techniques and Equipment22

Phenomena and Processes53

Disciplines and Occupations1

Technology, Industry, Agriculture4

Information Science3

Health Care1

Plasma membrane8

Signaling pathway1

Kinase19

Superfamily9

Mutations13

GAPs5

GTPases13

Tumor7

Receptors7

Regulates4

Binds4

Intracellular8

Activator2

GEFs1

Gene encodes2

Hydrolysis3

Phosphorylation5

Negatively1

Guanine nucleo3

Actin5

Encodes2

Pathways9

Isoforms4

Stimulates2

Inactivation2

Inhibitor4

Effector proteins2

Downstream3

Subfamily2

Phosphorylates4

Receptor5

Regulators1

Cellular5

Oncogene2

RhoA7

Stabilized NOTCH1 which1

Progression1

Activity12

Small G proteins4

Nucleotide-exchange2

Family proteins1

Interactions2

Molecules1

Oncogenic2

Regulate3

Cdc424

Catalytic1

Integrin1

Inhibition5

Regulatory proteins1

Encode1

Molecular switches1

Neurofibromin5

Interaction4

Regulation4

Cancers3

Homologue1

Proliferation3

Genes5

Mitochondrial2

Activation3

Homology1

Differentially1