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  • Genes
  • For example, genes indicating cell cycle aberrations (cyclin D2, cyclin B1, activator of S-phase kinase, and the cell cycle checkpoint kinase, CHK1) and invasive-metastatic potential (matrix metalloproteinase 11, v-Ral, and integrin β 4 ) were highly expressed in tumor cells. (aacrjournals.org)
  • In contrast, genes underexpressed in tumors included genes involved in apoptosis (B-cell CLL/lymphoma 6, secretory leukocyte protease inhibitor, and calpastatin), cell structure (keratin 7 and carcinoembryonic antigen-related cell adhesion molecule 6), and putative tumor suppressor genes (H-Ras-like suppressor 3, retinoic acid receptor responder 1, and growth arrested specific 8) among others. (aacrjournals.org)
  • Although the frequency and distribution varies between RAS genes and cancer types, the vast majority of activating RAS mutations occur at one of three residues - G12, G13 and Q61. (reactome.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)
  • Recently, a large number of genes encoding GTP-binding proteins and the proteins that interact with these molecular switches have been cloned and expressed. (embl-heidelberg.de)
  • In: Spandidos D.A. (eds) The Superfamily of ras-Related Genes. (springer.com)
  • We screened microarrays to identify cellular targets of this pathway, and found that genes upregulated by B-Raf/MKK/ERK showed highest association with cell cycle regulators, whereas genes downregulated were most highly associated with axon guidance genes, including plexin-semaphorin family members. (pubmedcentralcanada.ca)
  • epidermal
  • N-RAS activation can be induced by Epidermal growth factor ( EGF ) signaling [ 4 ]. (bio-rad.com)
  • Activated Epidermal growth factor receptor ( EGFR ) associates with SHC (Src homology 2 domain containing) transforming protein 1 ( Shc ) and Growth factor receptor-bound protein 2 ( GRB2 ) and this leads to Son of sevenless homolog ( SOS ) activation [ 5 ], [ 6 ]. (bio-rad.com)
  • Here, we show that in fibroblasts, insulin, epidermal growth factor (EGF) and serum activate ATF2 via a so far unknown two‐step mechanism involving two distinct Ras effector pathways: the Raf-MEK-ERK pathway induces phosphorylation of ATF2 Thr71, whereas subsequent ATF2 Thr69 phosphorylation requires the Ral-RalGDS-Src-p38 pathway. (embopress.org)
  • calcium
  • Any process that modulates the frequency, rate or extent of the binding or confining calcium ions such that they are separated from other components of a biological system. (princeton.edu)
  • The extracellular domain of E-Cadherin binds to Ca2+ (Calcium) and forms complexes with the extracellular domains of E-Cadherin molecules on neighboring cells. (sabiosciences.com)
  • adenomatous poly
  • IQGAP1 captures and stabilizes Microtubules/Tubulins through the Mt-BPs (Microtubule-Plus-End-Binding Proteins), APC (Adenomatous Polyposis Coli) and CLIP170 (Cytoplasmic Linker Protein-170Alpha-2), leading to establishment of polarized cell morphology and directional cell migration. (sabiosciences.com)
  • Activation of RAS
  • Activation of RAS has been implicated in mediating many aspects of the transformed phenotype, including deregulated proliferation, survival, invasion, and metastasis. (aacrjournals.org)
  • The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. (embl-heidelberg.de)
  • EGFR
  • To gain insight into possible modes of collateral sensitivity, we performed in silico molecular docking studies of honokiol to EGFR and EGFR-related downstream signal proteins. (thefreelibrary.com)
  • This indicates that collateral sensitivity of EGFR-transfectant cells towards honokiol may be due to binding to EGFR and downstream signal transducers. (thefreelibrary.com)
  • GTPases
  • Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to contribute to inflammation and joint destruction in RA, and abrogation of Ras family signaling is therapeutic in animal models of RA. (biomedcentral.com)
  • 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)
  • This is due to the extreme clinical relevance of the Ras family of small GTPases (H-Ras, K-Ras, and N-Ras), as they are the most commonly mutated oncogenes in human cancer, being present in 20% to 30% of all human tumors and K-Ras is mutated in up to 90% in pancreatic cancer [ 1 ]. (ijbs.com)
  • The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. (embl.de)
  • actin
  • The cytoplasmic domain of E-Cadherin associates with cytosolic proteins called Catenins (Alpha, Beta and p120), which in turn provide anchorage to the Actin cytoskeleton to form stable cell-cell contacts. (sabiosciences.com)
  • Ctnn-Alpha (Catenin-Alpha) binds to Ctnn-Beta and links components of the Adherens Junctions to the Actin cytoskeleton. (sabiosciences.com)
  • It also binds to Vcl (Vinculin), Zyx (Zyxin) and Alpha-Actn (Alpha-Actinin), which in turn binds to F-Actin. (sabiosciences.com)
  • Additional proteins and regulators of Actin polymerization such as the Actin-related protein, ARP2/3 complex also occur at the Adherens Junctions (Ref.1 & 2). (sabiosciences.com)
  • Cooperation of Cdc42 small G protein-activating and actin filament-binding activities of frabin in microspike formation. (pathwaymaps.com)
  • molecule
  • Ctnn-Beta (Catenin-Beta) binds through its armadillo repeats to the distal region of the E-Cadherin tail, thereby stabilizing the E-Cadherin molecule and facilitating transport of the newly synthesized protein to the cell surface. (sabiosciences.com)
  • Upon engagement of the T cell receptor ( TCR alpha/beta - CD3 complex ) by antigen presented on Major histocompatibility complex, class II ( MHC class II ) molecules, CD4 molecule ( CD4 )-bound Lymphocyte-specific protein tyrosine kinase ( Lck ) is activated and proceeds to phosphorylate CD247 molecule ( CD3 zeta ). (bio-rad.com)
  • ubiquitin
  • The level of junction proteins at the site of cell-cell contacts is modulated by transcriptional regulation and/or protein degradation through the Ubiquitin-Proteasome pathway. (sabiosciences.com)
  • It binds to tyrosine phosphorylated E-Cadherins and facilitates the internalization and subsequent Ubiquitin-dependent degradation of E-Cadherins. (sabiosciences.com)
  • E-Cadherin bound to Hakai may initiate the activation of intracellular signaling pathways, whereas the E3-ligase function of Hakai mediates the transfer of Ubiquitin chains to E-Cadherin and Ctnn-Beta through the E1-E2 ubiquitination system. (sabiosciences.com)
  • pathway
  • Many thanks for your valuable input into the RAS pathway diagram. (cancer.gov)
  • Michael Tainsky ( mat@wayne.edu ) noted that AP2 is essential for RAS transformation, but I couldn't find a direct link to the RAS pathway. (cancer.gov)
  • Mutated Ras proteins remain longer in their active form than normal Ras proteins, resulting in an overstimulation of the proliferative pathway. (embl.de)
  • inhibitor
  • Similar binding affinities of AKT, MEK1, MEK2, STAT3 and mTOR were calculated for honokiol (range from -9.0 [+ or -]0.01 to 7.40 [+ or -]0.01 kcal/mol) compared to corresponding control inhibitor compounds for these signal transducers. (thefreelibrary.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)