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  • catalytic
  • Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. (qmul.ac.uk)
  • oncogenic
  • However, oncogenic K-Ras mt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. (ijbs.com)
  • However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. (ijbs.com)
  • The mechanism involves increased activity of oncogenic K-Ras mt . Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Ras mt is now known to not be constitutively active. (ijbs.com)
  • Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Ras mt . Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Ras mt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. (ijbs.com)
  • Oncogenic mutation of RAS results in aberrant cellular signaling and is responsible for more than 30% of all human tumors. (aacrjournals.org)
  • MAPK
  • The Ets transcription elements, Ets1 and Ets2, are MAPK substrates and regulate the transcription of genes that harbor GGAA/T motif-containing regulatory areas . (bioentryplus.com)
  • Moreover, we show that the potentiating effect of ionomycin on Ras-GRF-mediated MAPK stimulation is also regulated by Cdc42. (hud.ac.uk)
  • proline-rich
  • A well established mechanism for the membrane recruitment of Sos involves the formation of a ternary complex with the activated RTK and the adaptor molecule Grb2, through the binding of the Grb2 SH3 domain to a proline-rich sequence in the C-terminus of Sos. (patentsencyclopedia.com)
  • homology domain
  • In Vivo Functional Analysis of the Ras Exchange Factor Son of Sevenless," Science 268:576-579 (1995)), and genetic and biochemical studies have implicated the Sos N-terminal pleckstrin homology domain (Sos-PH) as the critical determinant (McCollam et al. (patentsencyclopedia.com)
  • Furthermore
  • Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. (ijbs.com)
  • lipid
  • Our results suggest that ERMES is not a passive conduit for interorganellar lipid exchange, but that it can be regulated in response to physiological needs. (pnas.org)
  • In ERMES, the three SMP domains may be aligned to provide a hydrophobic slide bridging the aqueous gap between the ER and OMM to allow interorganellar lipid exchange ( 5 ). (pnas.org)
  • ERMES has been implicated in biological roles extending beyond lipid exchange. (pnas.org)
  • mutants
  • Analysis of TSC1 binding defective mutants of TSC2 shows that TSC1 is not required for the TSC2 GAP activity but may function as a regulatory component in the TSC1/TSC2 complex. (asm.org)
  • activity
  • guanine nucleotide exchange factor RasGRP1 inhibited Rhes-mediated control of striatal motor activity in mice. (nih.gov)
  • Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. (ijbs.com)
  • Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. (ijbs.com)
  • Nevertheless, recent observations have shed a new light on the mechanisms involved in Ras mediated oncogenesis that emphasize the importance of Ras activity. (ijbs.com)
  • RHEB
  • We found that Arg15, a residue equivalent to Gly12 in Ras, is important for Rheb to function as a substrate for TSC2 GAP. (asm.org)
  • We demonstrated a novel catalytic mechanism of the TSC2 GAP and Rheb that TSC2 uses a catalytic "asparagine thumb" instead of the arginine finger found in Ras-GAP. (asm.org)
  • cytoplasmic
  • By immunofluorescence, Ras-GRF1 exhibits a predominant cytoplasmic distribution, particularly at the perinuclear area, and mostly excluded from lamelipodia and peripheral structures. (atlasgeneticsoncology.org)