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  • guanyl-releasi
  • RAS guanyl-releasing protein 1 (RASGRP1) deficiency has recently been shown to cause a primary immunodeficiency (PID) characterized by CD4 + T cell lymphopenia and Epstein-Barr virus (EBV)-associated B cell lymphoma. (springer.com)
  • CDC25
  • In Saccharomyces cerevisiae, the product of the CDC25 gene controls the RAS-mediated production of adenosine 3',5'-monophosphate (cAMP). (sciencemag.org)
  • This review discusses the structure and function of the catalytic or CDC25 homology domain common to almost all Ras-family GEFs. (nih.gov)
  • RasGRP1 possesses a catalytic region consisting of a REM (Ras exchange motif) and a CDC25 (cell division cycle 25) domain. (biochemsoctrans.org)
  • pathways
  • 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. (bio-rad.com)
  • The Ras-cyclic AMP pathway is connected to other nutrient-regulated signaling pathways and mediates the global stress responses of Saccharomyces cerevisiae. (pomposity.us)
  • Here, we show that Rom2p, the Rho1 GTP/GDP exchange factor, can mediate stress responses and cell growth via the Ras-cAMP pathways. (pomposity.us)
  • regulate
  • Taken together, our data indicate that Rom2p can regulate PKA activity by controlling cAMP levels via the Ras-cAMP pathway and that for those stresses related to oxidative stress, this cross-talk is probably mediated via the Rho1p-activated MAPK pathway. (pomposity.us)
  • MAPK
  • We show that GDP- but not GTP-bound Cdc42 prevents Ras-GRF recruitment to the membrane and activation of Ras/MAPK, although no direct association of Ras-GRF with Cdc42 was detected. (hud.ac.uk)
  • We also demonstrate that catalyzing GDP/GTP exchange on Cdc42 facilitates Ras-GRF-induced MAPK activation. (hud.ac.uk)
  • Moreover, we show that the potentiating effect of ionomycin on Ras-GRF-mediated MAPK stimulation is also regulated by Cdc42. (hud.ac.uk)
  • As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. (upm.edu.my)
  • cascade
  • In addition, overexpression of ROM2 could not rescue cells lacking the regulatory subunit of PKA, indicating that the Ras-adenylate, cyclase-PKA cascade is essential for Rom2p-mediated stress responses and cell growth. (pomposity.us)
  • apoptosis
  • Ras is a membrane-bound small GTPase that plays a pivotal role in transducing responses to diverse extracellular signals that impact various cellular processes, prominently cell proliferation, differentiation, apoptosis ( 1 ). (frontiersin.org)
  • homology domain
  • Here, we investigate the exchange factor activity of the Dbl-homology domain containing constructs of the adaptor protein Intersectin1L (ITSN1L), which is a specific GEF for Cdc42. (genes2cognition.org)
  • GTPase
  • Immunoblotting and active Ras pull-down assays confirmed perturbed ERK1/2 signaling and reduced Ras-GTPase activity in heterologous Jurkat cells with ectopic expression of RASGRP1 mutants. (springer.com)
  • ROM2 was isolated as a suppresser of heat and NaCl sensitivity caused by the lack of the Ras-GTPase activator Ira2p or of cAMP phosphodiesterases. (pomposity.us)
  • assays
  • Despite their importance, detailed kinetic or comparative studies of family members are rarely undertaken due to the lack of real-time assays measuring nucleotide binding or exchange. (unm.edu)
  • Using a dynamics-based pocket identification scheme, ensemble docking, and innovative cell-based assays, here we show that andrographolide (AGP)-a bicyclic diterpenoid lactone isolated from Andrographis paniculata-and its benzylidene derivatives bind to transient pockets on Kirsten-Ras (K-Ras) and inhibit GDP-GTP exchange. (upm.edu.my)
  • mutant
  • However, it is unclear whether, or how, these ligands could lead to drugs that act against constitutively active oncogenic mutant Ras. (upm.edu.my)
  • Importantly, our findings not only show that nucleotide exchange factors are required for oncogenic Ras signaling but also demonstrate that inhibiting nucleotide exchange is a valid approach to abrogating the function of oncogenic mutant Ras. (upm.edu.my)
  • The selectivity in nucleotide exchange kinetics for GDP over GTP is even more pronounced when a Cdc42 mutant, F28L, is used, which is characterised by fast intrinsic dissociation of nucleotides. (genes2cognition.org)
  • Deletion of IRA2 exacerbated the freeze-thaw sensitivity and growth defect of the rom2 mutant, indicating that Rom2p signaling may control Ras independently of IRA2. (pomposity.us)
  • bind
  • Recently, several smallmolecule ligands have been discovered that directly bind Ras and inhibit its function by interfering with exchange factor binding. (upm.edu.my)
  • In sum, the combined analysis of our computational and cell biology results show that AGP derivatives directly bind Ras, block GDP-GTP exchange, and inhibit both wild-type and oncogenic K-Ras signaling. (upm.edu.my)
  • novel
  • Over the past 5 years, approximately 20 novel Ras-family GEFs have been identified and characterized. (nih.gov)
  • tumor
  • Moreover, GO-203 treatment of H1975 (EGFR L858R/T790M) and A549 (K-Ras G12S) xenografts growing in nude mice resulted in tumor regressions. (aacrjournals.org)
  • gene
  • Partially purified preparations of the carboxy-terminal domain of the SCD25 gene product enhanced the exchange rate of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) of pure RAS2 protein by stimulating the release of GDP. (sciencemag.org)
  • RasGRF1 expression was manipulated in RA FLS by cDNA transfection and gene silencing, and effects on MMP-1, TIMP-1, MMP-3, IL-6, and IL-8 production measured by ELISA. (biomedcentral.com)
  • positively
  • Production of MMP-1 and MMP-3 in RA but not non-RA synovial tissue positively correlated with expression of RasGRF1 and co-localized in cells expressing RasGRF1. (biomedcentral.com)
  • activity
  • Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. (frontiersin.org)
  • These results provide the first evidence for the involvement of a Rho family G protein in the control of the activity of a Ras exchange factor. (hud.ac.uk)
  • The higher exchange activity of ITSN1L towards the GDP-bound conformation of Cdc42 could represent an evolutionary adaptation of this GEF that ensures nucleotide exchange towards the formation of the signalling-active GTP-bound form of Cdc42 and avoids dissociation of the active complex. (genes2cognition.org)
  • family
  • Here we report a bead-based flow cytometric assay that quantitatively measures the nucleotide binding properties of glutathione-S-transferase (GST) chimeras for prototypical Ras family members Rab7 and Rho. (unm.edu)
  • adhesion
  • These data indicate that a variety of different signaling mechanisms can be induced to activate Ras, enabling tyrosine kinases, G-protein-coupled receptors, adhesion molecules, second messengers, and various protein-interaction modules to relocate and/or activate GEFs and elevate intracellular Ras-GTP levels. (nih.gov)
  • RasGRP2 acts on the Ras-related protein Rap and functions in platelet adhesion. (biochemsoctrans.org)
  • vitro
  • This protein was shown to activate H-Ras in a cation-dependent manner in vitro. (bio-rad.com)
  • cells
  • Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases (MMPs). (biomedcentral.com)