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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)
  • Sos1
  • RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and restricts intestinal epithelial cell growth. (nih.gov)
  • SOS1, a Ras GEF, binds through its PxxP motif (amino acids [a.a.] 1021-1034) to Crk/CrkL, and knockdown of SOS1 inhibits Crk-mediated transformation of NIH3T3 cells and migration of HEY (ovarian carcinoma) cells [ 16 , 17 ]. (ijbs.com)
  • Here, we describe how pharmacologically targeting SOS1 induced biphasic modulation of RAS-GTP and ERK phosphorylation levels, which we observed in a variety of cell lines expressing different RAS-mutant isoforms. (aacrjournals.org)
  • We show that compound treatment caused an increase in phosphorylation at ERK consensus motifs on SOS1 that was not observed with the expression of a non-phosphorylatable S1178A SOS1 mutant or after pretreatment with an ERK inhibitor. (aacrjournals.org)
  • Furthermore, in cells expressing either S1178A SOS1 or a constitutively membrane-bound CAAX box tagged SOS1 mutant, we observed elevated RAS-GTP levels over time in response to compound, as compared with the biphasic changes in RAS-GTP exhibited in cells expressing wild-type SOS1. (aacrjournals.org)
  • These results suggest that small molecule targeting of SOS1 can elicit a biphasic modulation of RAS-GTP and phospho-ERK levels through negative feedback on SOS1 that regulates the interaction between SOS1 and GRB2. (aacrjournals.org)
  • kinase
  • The receptor tyrosine kinase ("RTK")-Ras signaling axis plays an essential role in the regulation of a wide array of cellular processes, including cell proliferation, differentiation, and survival (Schlessinger et al. (patentsencyclopedia.com)
  • Sevenless
  • and identifying candidate compounds which modulate binding of Son of sevenless to phosphatidic acid as compounds potentially effective in treating a condition mediated by Ras. (patentsencyclopedia.com)
  • Functional Roles for the Pleckstrin and Dbl Homology Regions in the Ras Exchange Factor Son-of-Sevenless," J. Biol. (patentsencyclopedia.com)
  • biochemical
  • Such a distribution can be ascertained by biochemical fractionation, which shows Ras-GRF1 in both soluble and particulate fractions, its proportions vary depending on the cell type. (atlasgeneticsoncology.org)
  • signals
  • Thus, Ras is generally not active until called upon by external cellular signals, but once activated it can influence multiple cellular functions. (ijbs.com)
  • activity
  • guanine nucleotide exchange factor RasGRP1 inhibited Rhes-mediated control of striatal motor activity in mice. (nih.gov)
  • Ras-GRF1, along with Ras-GRF2 and Sos, are the only known exchange factors that combine Rho and Ras exchanger activity in the same protein. (atlasgeneticsoncology.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)
  • 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)
  • 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)
  • 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)
  • interaction
  • This initial step of loading GTP is not spontaneous, but rather requires the interaction of Ras with activating molecules. (ijbs.com)
  • formin-2 formin SPIR interaction motif (FSI) complex. (ebi.ac.uk)