• 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)
  • These proteins play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. (antibodiesinc.com)
  • The GTPase superfamily: conserved structure and molecular mechanism. (xenbase.org)
  • Human RAS superfamily proteins and related GTPases. (xenbase.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)
  • 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)
  • The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. (bioss.com.cn)
  • One way SynGAP1 affects these processes is through the MAP kinase signaling pathway by attenuation of Ras signalling. (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)
  • In eukaryotes, cyclic AMP works by activating protein kinase A (PKA, or cAMP-dependent protein kinase ). (wikipedia.org)
  • Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus enabling those catalytic units to phosphorylate substrate proteins. (wikipedia.org)
  • Protein kinase A can also phosphorylate specific proteins that bind to promoter regions of DNA, causing increases in transcription. (wikipedia.org)
  • Several classes of protein kinases , including protein kinase C, are not cAMP-dependent. (wikipedia.org)
  • Further effects mainly depend on cAMP-dependent protein kinase , which vary based on the type of cell. (wikipedia.org)
  • Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. (embl.de)
  • The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain. (embl.de)
  • Here we report that EWS, a nuclear RNA-binding prooncoprotein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin. (embl.de)
  • 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)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • These guanosine triphosphatases bind GTP causing the activation of mitogen activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K) and Ras-like (RAL) pathways [ 1 ]. (biomedcentral.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • Some of these proteins, such as MEK, belong to the MAP-Kinase pathway and are critical regulators of cell proliferation and survival. (broadinstitute.org)
  • Results of their new study suggest that these malformations are a result of KRAS -induced activation of the mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signaling pathway in brain endothelial cells. (medscape.com)
  • In the process, the RAS pathway, which is overactive in SYNGAP1-associated intellectual disability is inhibited by statins. (wikipedia.org)
  • The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is frequently de-regulated in human cancer. (babraham.ac.uk)
  • RAS protein plays a vital role in the modulation of cell survival, proliferation, and differentiation by molecular pathway signaling. (encyclopedia.pub)
  • Our results demonstrate an association between cognitive impairment and a defect in a signalling pathway that depends on a Ras-like GTPase. (embl-heidelberg.de)
  • 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)
  • Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. (xenbase.org)
  • 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)
  • 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)
  • 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)
  • 2007), Evolution of the Rho family of ras-like GTPases. (xenbase.org)
  • GTPases of the Rho family are molecular switches that play important roles in converting and amplifying external signals into cellular effects. (xenbase.org)
  • The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. (embl-heidelberg.de)
  • 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)
  • Ras homology family 2 (Rho2) of small guanosine triphosphatases (GTPases). (umbc.edu)
  • 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)
  • 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)
  • 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)
  • These data suggest that PKC may regulate interactions of EWS and other RNA-binding proteins with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing. (embl.de)
  • TBC1D15 activated three novel oncogenic pathways to promote self-renewal, p53 loss, and Nanog transcription in TICs. (nature.com)
  • Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
  • Ras proteins are key molecular switches in cell signaling pathways that, when activated, trigger cell growth and division. (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)
  • 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)
  • These findings give a comprehensive view of the evolutionary canvas of the Rho family and provide guides for future structure and evolution studies of other components of Rho signaling pathways, in particular regulators of the RhoGEF family. (xenbase.org)
  • 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)
  • an adapter protein coupling the receptor to downstream signaling pathways. (bioss.com.cn)
  • Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. (embl.de)
  • The Rap2 subgroup is part of the Rap subfamily of the Ras family. (nih.gov)
  • Neurofibromin loss potentially hyperactivates classic Ras (H-Ras, N-Ras, K-Ras), M-Ras, and R-Ras (R-Ras, R-Ras2/TC21) subfamily proteins. (biomedcentral.com)
  • Cells were transfected with doxycycline-inducible vectors expressing either a pan-inhibitor of the R-Ras subfamily [dominant negative (DN) R-Ras] or enhanced green fluorescent protein (eGFP). (biomedcentral.com)
  • A cascade effect occurs when ras -GTPase is "switched on" by incoming signals, leading to activation of other proteins, which, in turn, activate genes responsible for cell growth and differentiation. (medscape.com)
  • Mutations in ras genes can cause permanent activation of ras proteins. (medscape.com)
  • It regulates Sp7 protein expression and induces expression of major bone matrix protein genes, such as Col1a1, Spp1, Ibsp, Bglap2, and Fn1 ( 7 , 8 ). (frontiersin.org)
  • Gain-of-function variants in the three RAS genes have been found in 27 % of human cancers [ 3 ]. (biomedcentral.com)
  • The degree of activation and the underlying biochemical mechanism differs between variants in the three RAS genes, with the KRAS isoform being the most commonly disrupted in human carcinomas [ 6 ]. (biomedcentral.com)
  • The 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)
  • This domain occurred 99 times on human genes ( 174 proteins). (umbc.edu)
  • Genetic studies have clarified that most microcephaly genes encode ubiquitous proteins involved in mitosis and in maintenance of genomic stability, but the effects of their inactivation are particularly strong in neural progenitors. (cancerindex.org)
  • The RAB3GAP1 , RAB3GAP2 , and TBC1D20 genes provide instructions for making proteins that regulate the activity of this protein. (medlineplus.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)
  • Mutations that produce abnormally active Ras proteins are common in human cancers, particularly those of the pancreas, lung, and colon. (cshlpress.com)
  • Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. (rcsb.org)
  • Oncogenic mutations result in functional activation of Ras family proteins by impairing GTP hydrolysis. (rcsb.org)
  • KRAS is one of the most highly mutated proteins in cancer accounting for nearly 30% of cancer related mutations, and 86% of all RAS related mutations (reviewed in (1, 2)) . (cytoskeleton.com)
  • Mutations to codon 12 in KRAS maintains kRAS in an active, GTP-bound state through preventing GTPase-activating proteins (GAP) association. (cytoskeleton.com)
  • Mutations of the NF1 gene potentially results in the activation of multiple Ras proteins, which are key regulators of many biologic effects. (biomedcentral.com)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Mutations that cause Warburg micro syndrome completely eliminate the production or function of the protein produced from the gene. (medlineplus.gov)
  • Mutations that result in Martsolf syndrome reduce but do not eliminate protein function. (medlineplus.gov)
  • In collaboration with a group at the University of Geneva (Dr S.I. Nikolaev and Dr S.E. Antonarakis) and the group of Dr J.E. Fish from University of Toronto, they performed exome DNA sequencing of the tissue samples of 26 patients and found somatic activating KRAS mutations in some of them. (medscape.com)
  • In total, the researchers detected somatic activating KRAS mutations in tissue samples from 45 of 72 patients and in none of the 21 paired blood samples. (medscape.com)
  • This gives GTP an advantage over GDP and increases the proportion of active GTP-bound Ras. (rcsb.org)
  • The RAS family consists of three proteins all sharing a highly conserved N-terminus region: Harvey RAS (HRAS), Kirsten RAS (KRAS) and neuroblastoma RAS (NRAS). (biomedcentral.com)
  • In 1998 a family of cAMP-sensitive proteins with guanine nucleotide exchange factor (GEF) activity was discovered. (wikipedia.org)
  • 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)
  • Synaptic Ras GTPase-activating protein 1, also known as synaptic Ras-GAP 1 or SYNGAP1, is a protein that in humans is encoded by the SYNGAP1 gene. (wikipedia.org)
  • The NF1 gene product is a cytoplasmic protein called neurofibromin 1, which appears to have diverse functions in many different tissues. (medscape.com)
  • 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)
  • In 1986, the NF2 gene was mapped to chromosome 22, and in 1993, two groups independently isolated the gene and named its encoding protein merlin or schwannomin. (bmj.com)
  • Rho GTPase-activating protein p115 or ARHGAP4 is encoded by the gene ARHGAP4 and is a member of the RHO GTPase-activating proteins (rhoGAP) family of proteins. (antibodiesinc.com)
  • 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)
  • Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. (xenbase.org)
  • approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. (cam.ac.uk)
  • This gene encodes a large protein that functions as a GDP to GTP exchange factor. (cancerindex.org)
  • What does this gene/protein do? (cancerindex.org)
  • Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. (bioss.com.cn)
  • This gene encodes a member of the regulator of G-protein signaling family. (raybiotech.com)
  • The RAB18 gene provides instructions for making the RAB18 protein. (medlineplus.gov)
  • 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 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)
  • [1] Adenylate cyclase is activated by a range of signaling molecules through the activation of adenylate cyclase stimulatory G ( G s )-protein-coupled receptors. (wikipedia.org)
  • Inhibition of R-Ras/R-Ras2 and ROCK1 signaling also triggered the accumulation of abnormal intracellular vesicles, indicating that these signaling molecules regulate the movement of proteins and other molecules in the cellular interior. (biomedcentral.com)
  • Non-malignant somatic KRAS variants underlie a subset of RAS-associated autoimmune leukoproliferative disorders (RALD). (biomedcentral.com)
  • This case of idiopathic splenomegaly in childhood due to a somatic variant in KRAS expands our understanding of the clinical spectrum of RAS-associated autoimmune leukoproliferative disorder and emphasizes the value of securing a molecular diagnosis in children with unusual early-onset presentations with a suspected monogenic origin. (biomedcentral.com)
  • 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)
  • Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. (rcsb.org)
  • This process is usually regulated by guanine nucleotide-exchange factors GTPase-activating proteins and guanine nucleotide-dissociation inhibitors (1). (sciencepop.org)
  • While efforts continue to develop direct small GTPase inhibitors a PLCG2 promising and more conventional Olmesartan medoxomil therapeutic approach has been to block the activities of RHO GTPase effectors. (sciencepop.org)
  • The active subunits catalyze the transfer of phosphate from ATP to specific serine or threonine residues of protein substrates. (wikipedia.org)
  • Association of the proto-oncogene product dbl with G protein betagamma subunits. (embl-heidelberg.de)
  • Here, we show the association of Dbl with G protein betagamma subunits (Gbetagamma) in transient co-expression and cell-free systems. (embl-heidelberg.de)
  • The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. (raybiotech.com)
  • This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. (raybiotech.com)
  • 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)
  • In this manner the neurons strike a "balance" that allows for neurons to become activated and convey discrete synaptic signals, while preventing excessive excitation. (frontiersin.org)
  • Meanwhile, the DOC-2/DAB2 interacting protein DAB2IP was previously identified as a member of the Ras-GTPase activating protein family, and functions as a tumor suppressor in cancer progression 7 , 8 . (nature.com)
  • The oncogenic role of TLR4 activated by endotoxin has been confirmed by others in a different liver tumor model 10 . (nature.com)
  • Consequently, overactive ras -GTPase signaling leads to tumor growth. (medscape.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)
  • 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)
  • Here we report the development of small molecules that irreversibly bind to a common oncogenic mutant, K-Ras(G12C). (rcsb.org)
  • 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)
  • Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. (embl.de)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • When ARF family proteins are activated, they bind to effector molecules, which in turn mediate downstream functions. (biomedcentral.com)
  • Targeting RAS directly is difficult because of the absence of known allosteric regulatory sites, as well as the fact that it has picomolar affinity to GTP/GDP (3) . (cytoskeleton.com)
  • Additionally, reproductive hormones regulate RAS activity in the cellular physiological function of ovarian follicles during pre-ovulatory maturation and ovulation. (encyclopedia.pub)
  • 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)
  • SynGAP1 is a complex protein with several functions that may be regulated temporally via complex isoforms. (wikipedia.org)
  • 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)
  • 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)
  • Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. (nih.gov)
  • 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)
  • glycosylated lysosomal membrane protein. (gsea-msigdb.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)
  • abstract = "The DOC-2/DAB2 interactive protein (DAB2IP) is a new member of the Ras GTPase-activating protein family. (elsevierpure.com)
  • This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. (biomedcentral.com)
  • RGK proteins have been implicated in mediating cytoskeletal rearrangements [2C5] and inhibition of voltage-gated calcium channel currents [6C10]. (health-ground.com)
  • Consistent with classical Ras inhibition, DN R-Ras and R-Ras2 knockdown inhibited proliferation. (biomedcentral.com)
  • However, DN R-Ras inhibition impaired migration and invasion but not survival. (biomedcentral.com)
  • Inhibition of R-Ras action inhibited proliferation, migration and invasion but not survival. (biomedcentral.com)
  • Among these effectors are several protein kinases that either are or might be amenable to small molecule inhibition. (sciencepop.org)
  • An amino-terminal portion conserved among a subset of Dbl family proteins is sufficient for the binding of Gbetagamma. (embl-heidelberg.de)
  • R-Ras2 was uniformly expressed in MPNST cells, with R-Ras present in a major subset. (biomedcentral.com)
  • Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. (embl.de)
  • Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. (embl.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)
  • Mass spectrometry-based phosphoproteomics identified thirteen protein networks distinctly regulated by DN R-Ras, including multiple networks regulating cellular movement and morphology. (biomedcentral.com)
  • 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)
  • 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)
  • These are termed Exchange proteins activated by cAMP (Epac) and the family comprises Epac1 and Epac2 . (wikipedia.org)
  • Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. (embl-heidelberg.de)
  • [ 3 ] The neurofibromin 1/ ras -GTPase connection has roles in the control of cell proliferation and the suppression of cell overgrowth. (medscape.com)
  • Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. (bioss.com.cn)
  • 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)
  • EGFR is a cell surface protein that binds to epidermal growth factor. (bioss.com.cn)
  • 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)
  • Recently, a drug that targets mutant RAS G12C specifically has shown promising clinical results and is now the first FDA approved RAS-targeting drug for the treatment of NSCLC, read on for a summary of this drugs journey from discovery to approval, and roadblocks that still lie ahead. (cytoskeleton.com)
  • Apart from the catalytic domain in the middle of the molecule, all Gap1 family members share two N-terminal C2 domains and a C-terminal extended PH domain. (sdbonline.org)
  • It is also involved in the activation of protein kinases . (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • Molecular genetic testing is useful in uncertain or questionable cases, as well as for prenatal diagnosis and for screening family members of an affected individual. (medscape.com)
  • With diminished regulation by GTPase activity, the nucleotide state of Ras becomes more dependent on relative nucleotide affinity and concentration. (rcsb.org)
  • In particular, we propose that Arg 85 and Asn 194 are involved in binding G proteins and enhancing GTPase activity. (embl-heidelberg.de)
  • 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)
  • Its activity is directed by intracellular signals mediated by various types of receptors such as G protein-coupled receptors. (embl-heidelberg.de)
  • 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)
  • These cancers can be difficult to treat because Ras oncoproteins have long been considered undruggable. (cshlpress.com)
  • Trio and its homologue UNC-73 are unique within the Dbl family insomuch as they encode two distinct DH/PH domain modules. (embl-heidelberg.de)
  • Runx2 belongs to the Run family and is an essential upstream transcription factor during osteoblast differentiation. (frontiersin.org)
  • Osterix (OSX) is a transcription factor in the SP family, which is essential for osteoblast differentiation, and its expression is closely related to Runx2 ( 9 ). (frontiersin.org)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • In addition, cAMP binds to and regulates the function of ion channels such as the HCN channels and a few other cyclic nucleotide-binding proteins such as Epac1 and RAPGEF2 . (wikipedia.org)
  • Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)