• Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP. (wikipedia.org)
  • Proteins that act as GDS can be classified into at least two families, on the basis of sequence similarities, the CDC24 family (see InterPro: IPR001331) and this CDC25 (RasGEF) family. (wikipedia.org)
  • The size of the proteins of the CDC25 family range from 309 residues (LTE1) to 1596 residues (sos). (wikipedia.org)
  • This domain has been shown, in CDC25 an SCD25, to be essential for the activity of these proteins. (wikipedia.org)
  • Cytoskeleton is the pre-eminent supplier of Rho and Ras family small G-proteins (SGPs). (cytoskeleton.com)
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (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)
  • Epac proteins also bear a Ras-associating (RA) domain name, which is present in several Ras-interacting proteins. (researchensemble.com)
  • All NSP proteins contain an NH 2 -terminal SH2 (Src homology domain 2) domain, a central proline/serine-rich domain, and a COOH-terminal domain with modest homology to Ras subfamily GDP-exchange factors (GEFs). (molvis.org)
  • A CDC25 homology domain name (CDC25HD) in the C-terminal catalytic domain name exhibits GEF activity for Ras-like GTPases [9]. (researchensemble.com)
  • Transformation by v-Src: Ras-MAPK and PI3K-mTOR mediate parallel pathways. (embl.de)
  • This suggests that other Ras-independent pathways contribute to transformation by v-Src. (embl.de)
  • To address the possibility that activation of phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR/FRAP), represents one of these pathways, we have examined the effect of simultaneous inhibition of the Ras-MAPK and PI3K-mTOR pathways on transformation of CEF by v-Src. (embl.de)
  • 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 Rasd1 protein is a dexamethasone induced monomeric Ras-like G protein that oscillates in the suprachiasmatic nucleus (SCN). (biomedcentral.com)
  • New strategies of HDL cholesterol ester transfer protein C-related hydrophobic lipid mediators exchange between GSK1292263 molecular weight HDL and apoB-containing lipoproteins. (vegfinhibitors.com)
  • 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)
  • However, simultaneous inhibition of signaling by the Ras-MAPK pathway and the PI3K-mTOR pathway essentially blocked transformation. (embl.de)
  • 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)
  • 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)
  • Here, we describe the first transgenic mouse model for activation of K-RAS in the lung in a RASSF1A-defective background. (cancerindex.org)
  • Osphorylates and active kinases, which in turn right phosphorylate and inactivate 1 of the a few members from the loved ones of CDC25 in the dephosphorylation and activation of cyclin-dependent-Dependent S3I-201 price kinase-dependent-Dependent cell cycle w W While Phasen? (vegfinhibitors.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)
  • An increase in the level of active, GTP-bound Ras is not necessary for transformation of chicken embryo fibroblasts (CEF) by v-Src. (embl.de)
  • A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. (embl.de)
  • This entry represents the catalytic domain of the Ras guanine-nucleotide exchange factors. (embl.de)
  • In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. (embl.de)
  • 1. Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function. (nih.gov)
  • 7. Mechanism of the guanine nucleotide exchange reaction of Ras GTPase--evidence for a GTP/GDP displacement model. (nih.gov)
  • 11. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence. (nih.gov)
  • 16. Raf-1 is involved in the regulation of the interaction between guanine nucleotide exchange factor and Ha-ras. (nih.gov)
  • 17. Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS. (nih.gov)
  • The son of sevenless (SOS) is a guanine nucleotide exchange factor (GEF) that exchanges GDP by GTP and activates Ras. (nih.gov)
  • The biological activity of RasGRF1 CDC25 domain can be determined from its ability to catalyze nucleotide exchange on Ras isoforms using the nucleotide exchange assay of Bodipy-GDP for excess GDP or GTP. (cytoskeleton.com)
  • The catalytic region has the CDC25-homology domain, which is responsible for the guanine-nucleotide exchange activity, and the Ras exchange motif (REM), which stabilizes the catalytic helix of CDC25HD, and the Ras-association (RA) domain, which is a protein interaction motif. (pancreapedia.org)
  • A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. (umbc.edu)
  • Evolutionarily conserved Dock family guanine nucleotide exchange factors (GEFs) activate Rac or Cdc42 GTPases through a unique dock homology region 2 domain to promote cytoskeletal rearrangements (26 -28). (tam-receptor.com)
  • RasGRF1 is a guanine exchange factor with selectivity for H-, K-, N- and R-Ras, which mediates Ras isoform activation under a variety of conditions and has been associated with multiple diseases (reviewed in 1, 2). (cytoskeleton.com)
  • The biological activity of N-Ras can be determined from the ability of the RasGRF1 exchange domain (Ras-GRF1-ExD) to catalyze the exchange of GDP for GTP on N-Ras. (cytoskeleton.com)
  • 10. Mechanism of free radical nitric oxide-mediated Ras guanine nucleotide dissociation. (nih.gov)
  • SOS has two Ras binding sites: Ras exchanger motif (Rem) domain (Ras allosteric site) and catalytic Cdc25 domain (Ras active site). (nih.gov)
  • The C-terminal region contains a CDC25-homology domain, a REM (Ras Exchange Motif) and a RA (Ras Association) domain. (pancreapedia.org)
  • Here the crystal structure of the catalytic module of Rlf consisting of a REM- and a CDC25-homology domain is determined. (rcsb.org)
  • The structure consists of two distinct alpha helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. (embl.de)
  • p140-RAS GRF (cdc25Mm) from mammals. (embl.de)
  • Differential actions of p60c-Src and Lck kinases on the Ras regulators p120-GAP and GDP/GTP exchange factor CDC25Mm. (embl.de)
  • 1998) and are discussed in relation to partial loss-of-function mutations and the specificity of Ras versus Rap binding. (embl-heidelberg.de)
  • When the GTP-bound Ras binds to the Rem domain, it relieves the steric occlusion and thereby activates SOS. (nih.gov)
  • Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos. (embl.de)
  • 18. Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme. (nih.gov)
  • 14. Conformational Dynamics Allows Sampling of an "Active-like" State by Oncogenic K-Ras-GDP. (nih.gov)
  • All known oncogenic mutants of Ras map to a small subset of amino acids. (embl.de)
  • As it still remains unclear how these phosphorylations can influence the Ras pathway we have analyzed the ability of p60c-Src and Lck to phosphorylate these two Ras regulators and have compared the activity of the phosphorylated and unphosphorylated forms. (embl.de)
  • Both kinases are shown to phosphorylate Cdc25 on the same sites. (readabstracts.com)
  • 8. Ras Binder Induces a Modified Switch-II Pocket in GTP and GDP States. (nih.gov)
  • Ras binding to the allosteric site induces conformational changes of SOS, leading to Ras activation. (nih.gov)
  • Evidences for a function of Raf-1 and phosphatidylinositol 3-kinase upstream to Ras. (nih.gov)
  • Chk1 kinase phosphorylates Cdc25, an activator of Cdc2. (readabstracts.com)
  • phosphorylation by Lck increased its capacity to stimulate the GDP/GTP exchange on Ha-Ras, whereas its phosphorylation by p60c-Src was ineffective. (embl.de)
  • One is the C-terminal Ras-associating domain bearing a structural homology with those of RalGDS and AF-6. (embl-heidelberg.de)
  • A standard biological assay for monitoring the biological activity of N-Ras is an exchange assay utilizing the 2X Exchange Buffer from the RhoGEF exchange assay kit (Cat. (cytoskeleton.com)
  • Mutants of Ras are found in 25-30% of human tumors. (embl.de)
  • Structural and biochemical analysis of Ras-effector signaling via RalGDS. (embl-heidelberg.de)
  • Ras is a prolific signalling molecule interacting with a spectrum of effector molecules and acting through more than one signalling pathway. (embl-heidelberg.de)
  • We have determined the minimal region of the budding yeast CDC25 gene capable of activity in vivo. (cshl.edu)
  • The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. (embl.de)
  • Structurally, the RA domain of RalGDS consists of a five-stranded mixed beta- sheet interrupted by a 12 residue alpha-helix and two additional small alpha- helices. (embl-heidelberg.de)
  • The major interaction between Ras and RalGDS RA domain occurs between two antiparallel beta-strands: beta 2 of Ras and beta 2 of RA. (embl-heidelberg.de)
  • The structure of the complex of Ras with the Ras-binding domain of its effector RalGDS (RGS-RBD), the first genuine Ras-effector complex, has been solved by X-ray crystallography. (embl-heidelberg.de)
  • Apo SOS is in an inactive state in which the Rem domain sterically obstructs the Ras binding site in the Cdc25 domain. (nih.gov)
  • The Cdc25 domain is now able to associate with the GDP-bound Ras and activates it. (nih.gov)
  • The DEP domain is involved in membrane targeting of the active molecule and the REM domain is participates in Ras activation when the two molecules are closely approximated. (pancreapedia.org)
  • Our previous study demonstrated that LPA could stimulate Rac activation, cytoskeleton reorganization, and ovarian cancer cell migration through a signaling pathway consisting of Ras-SOS1/EPS8/ABI1 tri-complex [ 14 ]. (biomedcentral.com)
  • Identification of PLC210, a Caenorhabditis elegans phospholipase C, as a putative effector of Ras. (embl-heidelberg.de)
  • Although crystal structure of Ras-SOS complex provided information of molecular interactions, the exact mechanism of the conformational changes of SOS and Ras activation remain unclear. (nih.gov)
  • Our goal is to simulate the SOS-Ras complex and sample the SOS conformational ensembles. (nih.gov)
  • In the nematode Caenorhabditis elegans, LIN-45 Raf has been identified by genetic analyses as an effector of LET-60 Ras. (embl-heidelberg.de)
  • Promotes the exchange of Ras-bound GDP by GTP. (nih.gov)
  • Gel filtration experiments show that the Ras x RGS-RBD complex is a monomer. (embl-heidelberg.de)
  • The results are compared to a recently determined structure of a similar complex using a Ras mutant (Huang et al. (embl-heidelberg.de)
  • Arfs are ubiquitous in eukaryotes, are very highly conserved both structurally and functionally, and exchange guanine nucleotides in a complex, highly regulated fashion that is sensitive to lipids, salts, and divalent metals. (nih.gov)