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  • kinase
  • The guanosine triphosphate (GTP)-loaded form of the guanosine triphosphatase (GTPase) Ras initiates multiple signaling pathways by binding to various effectors, such as the kinase Raf and phosphatidylinositol 3-kinase (PI3K). (sciencemag.org)
  • Consequently, much interest has centered on the binding partners of Ras, including the Ras-binding domain (RBD) of Raf kinase. (embl-heidelberg.de)
  • This review summarizes recent advances in our understanding of endothelial receptor tyrosine kinase endocytosis and signaling using vascular endothelial growth factor receptor-2 as a paradigm. (ahajournals.org)
  • mutations
  • The physiological importance of Ras' GTPase activity was recognized in the late 80s through the detection and biochemical characterization of GTPase impairing Ras mutations commonly found in various human tumor tissues ( 6 ). (frontiersin.org)
  • Based on the recent crystal structure of the complex of Rap1A with the Ras-binding domain of Raf, mutations were introduced in c-Raf-1 and their effects on Ras/Raf binding affinity in vitro and Ras/Raf regulated gene expression in vivo were analysed. (embl-heidelberg.de)
  • catalytic
  • 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-heidelberg.de)
  • A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. (embl-heidelberg.de)
  • Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. (qmul.ac.uk)
  • Rheb and TSC2 comprise a unique pair of GTPase and GAP, because Rheb has high basal GTP levels and TSC2 does not have the catalytic arginine finger found in Ras-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)
  • Oncogenic
  • Oncogenic mutated Ras is involved in almost all types of cancer and therefore an important target for the pharmaceutical industry. (csh-asia.org)
  • 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)
  • 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)
  • MAPK
  • Moreover, we show that the potentiating effect of ionomycin on Ras-GRF-mediated MAPK stimulation is also regulated by Cdc42. (hud.ac.uk)
  • 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)
  • 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)
  • Both genetic and biochemical studies have demonstrated that Rheb (Ras homolog enriched in brain) is a direct target of TSC2. (asm.org)
  • differentiation
  • 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)
  • inactivation
  • Neurite outgrowth from PC12 cells by basic fibroblast growth factor (bFGF) is mediated by RhoA inactivation through p190RhoGAP and ARAP3. (springer.com)
  • 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)
  • 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)
  • receptor
  • Among these, receptor tyrosine kinases (RTKs), such as vascular endothelial growth factor receptor-2 (VEGFR2) and fibroblast growth factor receptor-1 (FGFR1), are essential regulators of such essential EC activities as proliferation, migration, angiogenesis, and vascular permeability. (ahajournals.org)
  • regulatory
  • 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)
  • phosphodiesterases
  • 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)