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  • PI3K
  • RAF and PI3K), (iv) synthetic lethal interactors of mutant RAS, and (v) RAS-regulated metabolic processes in cancer cells. (sciencemag.org)
  • mTOR is a serine-threonine kinase that functions downstream of Ras and PI3K/AKT, and mTOR has been shown to be negatively regulated by NF1 ( 8 ). (aacrjournals.org)
  • 8 Ras has emerged as a convergent molecular switch that integrates and propagates extracellular signals to downstream cascades, the best characterized of which are the phosphatidylinositol-3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK) pathways. (ahajournals.org)
  • biochemical
  • The ability to temporally regulate Nf1 inactivation or Kras activation now enables us to examine the biochemical and cellular effects of hyperactive Ras in primary hematopoietic cells, including stem and progenitor populations. (ucsf.edu)
  • Judging from these changes and our biochemical data, we suggest the presence of an additional intermolecular contact surface in the lid-lock region of the protein. (proteopedia.org)
  • Early approaches considered for developing RAS inhibitors were guided by understanding the biochemical defects of mutant RAS proteins ( 5 ). (sciencemag.org)
  • These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. (frontiersin.org)
  • 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)
  • guanine nucleot
  • i) Molecules that directly bind RAS disrupt its interaction with guanine nucleotide exchange factors or with effectors such as the RAF serine-threonine kinases. (sciencemag.org)
  • 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)
  • In both the Ras·GDP and Ras·GTP states the nucleotide is very tightly bound ( 2 - 4 ) and for Ras activation to occur Ras guanine nucleotide exchange factors (RasGEFs) need to loosen the grip of Ras on the bound nucleotide, stabilizing nucleotide-free Ras that stochastically but preferentially associates with GTP, because GTP is present in the cell in higher concentrations than GDP ( 5 ). (frontiersin.org)
  • Guanine nucleotide exchange factors (GEFs) promote GTP-bound Ras state by enhancing exchange of GDP with GTP. (frontiersin.org)
  • Syngap1
  • De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. (nih.gov)
  • We provide evidence that truncating mutations in SYNGAP1 are common in NSID and can be also associated with autism. (nih.gov)
  • Par des techniques permettant la capture de l'exome et le séquençage de l'ADN génomique, notre laboratoire a précédemment reporté les premières mutations pathogéniques dans le gène à transmission autosomique dominante SYNGAP1. (umontreal.ca)
  • SYNGAP1 encode pour une protéine à activité GTPase pour Ras. (umontreal.ca)
  • Dans cette étude, nous avons confirmé que les patients pourvus de mutations dans SYNGAP1 présentent, entre autre, des phénotypes associés à des troubles comportementaux relatifs à la déficience intellectuelle. (umontreal.ca)
  • Ces résultats suggèrent que ces mutations faux-sens et tronquante résultent en la perte de la fonction de SYNGAP1 ayant fort probablement pour conséquences d'affecter la régulation du développement cérébral. (umontreal.ca)
  • sporadic
  • Analysis of sporadic astrocytomas and ependymomas demonstrates either increased rap1 or reduced/absent tuberin protein expression in 50%-60% of different cohorts of these gliomas, compared to 30%-33% of sporadic schwannomas and meningiomas and none of eight oligodendrocyte tumors. (sdbonline.org)
  • Characterisation of inherited and sporadic mutations in neurofibromatosis type-1. (proteopedia.org)
  • effectors
  • The success of this strategy requires cancer cells to have a differential molecular dependency on downstream effectors of Ras for survival, as compared with normal cells. (aacrjournals.org)
  • tumor suppressor
  • In this issue of Clinical Cancer Research , Parkin and colleagues report on the identification of a subset of adult acute myelogenous leukemia (AML), in which the tumor suppressor NF1 is functionally inactive, resulting in increased Ras signaling and sensitivity to mammalian target of rapamycin (mTOR) inhibition ( 1 ). (aacrjournals.org)
  • myeloid
  • K-Ras proteins containing this tandem duplication or a similar five amino acid E62_A66dup mutation identified in lung and colon cancers transform the growth of primary myeloid progenitors and of Ba/F3 cells. (sigmaaldrich.com)
  • downstream
  • In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells. (frontiersin.org)
  • receptor
  • Sap J, Munoz A, Damm K, The c-erb-A protein is a high-affinity receptor for thyroid hormone. (springer.com)
  • Multiple, yet distinct lipid products are generated following T cell receptor (TCR) stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. (frontiersin.org)
  • vertebrate
  • We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. (jove.com)
  • differentiation
  • Nf1 ablation also prevents bone morphogenic protein-2-induced osteoprogenitor differentiation and, consequently, expression of alkaline phosphatase and PPi breakdown, further contributing to PPi accumulation. (nih.gov)
  • 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)
  • Cancer
  • With the establishment of the RAS Initiative in 2013, the U.S. National Cancer Institute proclaimed a new war on RAS ( 4 ). (sciencemag.org)
  • localization
  • Deletion of sAnk1 did not change the expression and localization of SR proteins in 4-6 month old sAnk1 KO mice. (jove.com)
  • Persson H, Leder P. Nuclear localization and DNA binding properties of a protein expressed by human c-myc oncogene. (springer.com)
  • activity
  • In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23 / sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. (genetics.org)
  • NF1_HUMAN ] Stimulates the GTPase activity of Ras. (proteopedia.org)
  • NF1 shows greater affinity for Ras GAP, but lower specific activity. (proteopedia.org)
  • Critical
  • We identify Tyr32 in the Ras Switch I region as a critical residue that acts as a gate to the GTP binding site and which needs to be "open" during Ras coupling with GAP to allow for insertion of GAP residue Arg789. (gu.se)
  • novo
  • D'un autre côté, plusieurs études récentes suggèrent que des mutations de novo dans des gènes à transmission autosomique dominante, requis dans les processus de la plasticité synaptique peuvent être à la source d'une importante fraction des cas de déficience intellectuelle non syndromique. (umontreal.ca)
  • Ces dernières sont toutes de novo à l'exception de c.283dupC, héritée d'un père mosaïque pour la même mutation. (umontreal.ca)
  • mitochondrial
  • They identify and characterize a role for the CHCHD4 mitochondrial proteins in regulating HIF-α signaling, angiogenesis, and tumor progression. (jci.org)
  • human
  • Reddy EP, Reynolds RK, Santos E, Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. (springer.com)