Loading...
  • GTPases
  • These domains have been shown to interact with and regulate the activity of a number of small GTPases including direct binding of Rac1, Rnd1, and RhoD to the RBD and less-well defined sequestration of, or GAP activity against, R-Ras and Rap family members ( 4 - 6 ). (frontiersin.org)
  • The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors. (embl-heidelberg.de)
  • The three RAS genes encode four closely related small guanosine triphosphatases (GTPases, enzymes that hydrolyze guanosine triphosphate): HRAS, KRAS4A, KRAS4B, and NRAS. (sciencemag.org)
  • Ras family small GTPases play essential roles in a variety of cellular responses including cell proliferation, differentiation, survival, transformation, and tumor development [ 1 - 4 ]. (hindawi.com)
  • Apart from the classical Ras proteins, the only other member of the Ras subfamily of GTPases found to be mutated in human cancers was TC21 (also called R-Ras2) [ 15 ]. (hindawi.com)
  • The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. (embl.de)
  • However, physiological interaction between Lpd and Ras family GTPases still remains unclear, and the identity of which Ras family proteins directly bind to Lpd and function upstream of Lpd in neurons has been rarely understood. (jneurosci.org)
  • Catalytic subunit of the heterodimeric RalGAP2 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. (uniprot.org)
  • Cellular
  • Molecular and Cellular Biology , 19 (3) pp. 1928-1937. (ucl.ac.uk)
  • Cross Talk Between Cellular Redox State and the Antiapoptotic Protein Bcl-2. (nus.edu.sg)
  • The emerging evidence for the noncanonical activity linked to cellular redox metabolism provides a novel avenue for the design and development of diagnostic and therapeutic strategies against cancers refractory to conventional chemotherapy by the overexpression of this prosurvival protein. (nus.edu.sg)
  • Apart from Ras, they also target other cellular proteins that require farnesylation to become activated, e.g. (embl.de)
  • Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied so far indicates that the promotion of differentiation is the most prominent effect of Ras. (embl.de)
  • Thus, approaching such a complicated cellular response generates a more complex combination of molecular mechanisms, in which cell death, cellular damage, stress and repair are intermixed. (frontiersin.org)
  • For this reason, animal and cellular model systems are needed in order to dissect and clarify which molecular mechanisms have to be promoted and/or blocked. (frontiersin.org)
  • Genes
  • One of the genes responsible for this disorder is TSC2, located on human chromosome 16p, and encoding a 180 kDa protein (tuberin) that functions in part as a negative regulator of rap1. (sdbonline.org)
  • The well-validated role of mutationally activated RAS genes in driving cancer development and growth has stimulated comprehensive efforts to develop therapeutic strategies to block mutant RAS function for cancer treatment. (sciencemag.org)
  • RAS genes have the distinct honor of being the first mutated genes identified in human cancer, ushering in the era of molecularly targeted anticancer drug discovery. (sciencemag.org)
  • http://cancer.sanger.ac.uk/cosmic ), the three RAS genes constitute the most frequently mutated gene family in cancer, with RAS mutations found in ~25% of human tumors. (sciencemag.org)
  • The three human RAS genes are not mutated at equivalent frequencies in cancer. (sciencemag.org)
  • This has launched the development of novel anticancer agents, interfering with the proteins encoded by the identified mutated genes. (embl.de)
  • The Ras protein is involved in signal transduction: it passes on stimuli from extracellular factors to the cell nucleus, thereby changing the expression of a number of growth regulating genes. (embl.de)
  • differentiation
  • It was shown that Ras transduces signals from receptor-type tyrosine kinases to downstream effectors and thereby controls the proliferation and differentiation of various cell types [ 10 ]. (hindawi.com)
  • Ras proteins in the control of the cell cycle and cell differentiation. (embl.de)
  • Tumor
  • Mitochondria gained center stage in molecular oncology when Otto Warburg observed that tumor cells can ferment glucose to lactate even in the presence of oxygen, proposing that a failure in mitochondrial respiration was the cause of this metabolic trait, called aerobic glycolysis, and that this was in turn required for neoplastic growth ( 2 , 3 ). (frontiersin.org)
  • tyrosine
  • It was first reported to be expressed on T cells where it supports B cell development by binding to CD72, a low affinity receptor associated with the protein tyrosine phosphatase SHP-1 . (plos.org)
  • Receptor Protein-Tyrosine Kinases) RN - EC 3.6.1. (ucl.ac.uk)
  • processes
  • Brahma-related gene 1 inhibits proliferation and migration of human aortic smooth muscle cells by directly up-regulating Ras-related associated with diabetes in the pathophysiologic processes of aortic dissection. (springer.com)
  • Lpd was expressed in F-actin-rich distal dendritic processes and was required for both basal and M-Ras-mediated dendrite development. (jneurosci.org)
  • plexin
  • The cytoplasmic domain of each plexin contains a GTPase activation domain (GAP) of ∼600 aa encompassing a central Rac- or Rho-like binding motif (RBD) ( 2 , 3 ). (frontiersin.org)
  • mechanism
  • The second type appeared to be generated by a differential splicing mechanism and encoded a novel form of GAP with a predicted molecular mass of 100,400 daltons. (sciencemag.org)
  • hydrolysis
  • This may in turn be the cause of decreased GTP hydrolysis, and permanent "on" state of K-Ras, observed for these mutants. (gu.se)
  • localization
  • Mahalakshmi RN, Ng MY, Guo K, Qi Z, Hunziker W, Béguin P. Nuclear localization of endogenous RGK proteins and modulation of cell shape remodeling by regulated nuclear transport. (springer.com)
  • inactivation
  • Ras-induced epigenetic inactivation of the RRAD (Ras-related associated with diabetes) gene promotes glucose uptake in a human ovarian cancer model. (springer.com)
  • cancer
  • Studies have thus identified (onco)proteins (Bcl-2, STAT3/5, RAS, Rac1, and Myc) in manipulating ROS level as well as exploiting an altered redox environment to create a milieu conducive for cancer formation and progression. (nus.edu.sg)
  • FUTURE DIRECTIONS: Not only a heightened realization is required to unravel various gene/protein networks associated with cancer formation and progression, particularly from the redox standpoint, but there is also a need for developing more sensitive tools for assessing cancer redox metabolism in clinical settings. (nus.edu.sg)
  • Breast Cancer: A Molecular and Redox Snapshot. (nus.edu.sg)
  • With the establishment of the RAS Initiative in 2013, the U.S. National Cancer Institute proclaimed a new war on RAS ( 4 ). (sciencemag.org)
  • inhibition
  • Rad GTPase attenuates vascular lesion formation by inhibition of vascular smooth muscle cell migration. (springer.com)
  • Inhibition of Ras can be accomplished through inhibition of farnesyl transferase, the enzyme responsible for this modification. (embl.de)
  • Sema4D
  • Our previous studies on platelets showed that activated platelets also shed Sema4D and that the rate of shedding is relatively slow compared to platelet aggregation, requiring nearly 30 min to reach completion. (plos.org)
  • Subcellular fractionation showed M-Ras-dependent membrane translocation of Lpd, which was suppressed by Sema4D. (jneurosci.org)
  • UniProt
  • p>When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later. (uniprot.org)
  • Despite
  • Disappointingly, despite more than three decades of research effort, clinically effective anti-RAS therapies have remained elusive, prompting a perception that RAS may be undruggable. (sciencemag.org)
  • Despite more than 30 years of intensive efforts to develop pharmacologic inhibitors of RAS, a clinically effective anti-RAS therapy remains elusive ( 1 - 3 ). (sciencemag.org)
  • Despite the recent progress in identifying PSD proteins, several protein bands in the PSD fraction have remained unidentified, and the functions of the PSD are as yet incompletely understood. (jneurosci.org)
  • residues
  • The importance of two conserved arginine residues for catalysis by the ras GTPase-activating protein, neurofibromin. (embl-heidelberg.de)
  • The separate contributions of each of these residues to catalysis and binding affinity to Ras were measured. (embl-heidelberg.de)
  • These modified Ras proteins carry a number of different, natural and non-natural lipid residues, and the process was extended to also provide access to a number of fluorescently labeled derivatives. (embl.de)
  • arginine
  • We previously reported an important role for arginine methylation as a 'molecular switch' in regulating the disassembly of G3BP1 from the Dvl3-based supermolecular complexes ( Bikkavilli and Malbon, 2011 ). (biologists.org)
  • In the present study, we identified a role for arginine methylation and its substrate Ras GTPase-activating protein-binding protein 2 (G3BP2) in regulating Wnt3a-stimulated LRP6 phosphorylation. (biologists.org)