• A structural feature that distinguishes the Rho proteins from other small GTPases is the so-called Rho insert domain located between a β strand and an α helix within the small GTPase domain [ 1 - 3 ]. (biomedcentral.com)
  • Typically Rho proteins are 190-250 residues long and consist only of the GTPase domain and short terminal C-terminal extensions. (biomedcentral.com)
  • Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)
  • Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)
  • These genes encode for closely related GTPase proteins responsible for signal transduction within two main pathways, the mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase pathways, involved in the regulation of cell growth, survival, and differentiation. (oaepublish.com)
  • It is regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. (novusbio.com)
  • Protein prenylation is the posttranslational attachment of either a farnesyl group or a geranylgeranyl group via a thioether linkage (-C-S-C-) to a cysteine at or near the carboxyl terminus of the protein. (biomedcentral.com)
  • Polyisoprenylated cysteinyl amide inhibitors (PCAIs) are agents that mimic the essential posttranslational modifications of G-proteins. (oncotarget.com)
  • Protein prenylation, found in eukaryotes, is a posttranslational modification in which one or two isoprenoid groups are added to the C terminus of selected proteins using either a farnesyl group or a geranylgeranyl group. (umn.edu)
  • We have used specific inhibitors for farnesyltransferase (FTase) and geranylgeranyltransferase (GGTase) I as well as combinations of lovastatin with geranylgeraniol (GGOH) or farnesol (FOH) to investigate the role of protein prenylation in platelet-derived growth factor (PDGF)-induced PDGF receptor tyrosine phosphorylation. (nyu.edu)
  • Furthermore, although lovastatin, which inhibits both protein geranylgeranylation and protein farnesylation, blocked PDGF receptor tyrosine phosphorylation, co-treatment with GGOH, but not FOH, reversed the lovastatin block. (nyu.edu)
  • NIH-3T3 cells treated with the highly specific FTase inhibitor FTI-277 had no effect on PDGF receptor tyrosine phosphorylation or PDGF activation of mitogen-activated protein kinase (MAPK) at doses that completely inhibit FTase-dependent processing. (nyu.edu)
  • The RAS gene family, responsible for signal transduction within the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways, is frequently involved in carcinogenesis, and alterations in its member genes can be detected, with variable frequency, in a wide variety of solid and hematological cancers. (oaepublish.com)
  • The genes encoding CaaX protein prenyltransferases are considerably longer than those encoding non-CaaX subunits, as a result of longer introns. (biomedcentral.com)
  • The α subunits of protein prenyltransferases consist of tetratricopeptide repeats and are part of the tetratricopeptide repeat superfamily [ 5 ], which also includes functionally diverse proteins involved in transcription, co-chaperoning, protein transport, cell-cycle control and phosphorylation. (biomedcentral.com)
  • Substrates of the prenyltransferases include Ras, Rho, Rab, other Ras-related small GTP-binding proteins, G-protein γ-subunits, nuclear lamins, centromeric proteins and many proteins involved in visual signal transduction. (guidetopharmacology.org)
  • Small G-proteins, monomeric GTPases, or the RAS (Rat sarcoma) superfamily are a large family of small guanine nucleotide-binding proteins with molecular weights ranging from 20 to 30 kDa [ 1 , 2 ]. (oncotarget.com)
  • Prenylation facilitates protein localization mainly to the plasma membrane where the prenylated proteins, including small GTPases, mediate signal transduction pathways. (umn.edu)
  • Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. (biomedcentral.com)
  • In turn, GTP-bound active GTPases can interact with a plethora of different effectors which mediate the different cellular functions of this family of proteins. (biomedcentral.com)
  • Post-translational modification of proteins can be experimentally detected by a variety of techniques, including mass spectrometry, Eastern blotting, and Western blotting. (wikipedia.org)
  • printed on-line 14 Goal The year of 2010Redox factor-1 (Ref-1), any dual purpose health proteins along with Genetics restoring pursuits, plays a new cytoprotective purpose simply by post-translational redox customization of various transcribing components, such as hypoxia inducible factor-1 (HIF-1). (notes.io)
  • This Rac1 antibody was developed against a synthetic peptide from amino acid region 100-150 as a part of human Rac1 conjugated to blue carrier protein. (novusbio.com)
  • Thus, these results demonstrate that PDGF receptor tyrosine phosphorylation requires protein geranylgeranylation but not protein farnesylation and that the tyrosine phosphorylation levels of the receptor are modulated by a protein that is a substrate for GGTase I. (nyu.edu)
  • Many eukaryotic and prokaryotic proteins also have carbohydrate molecules attached to them in a process called glycosylation, which can promote protein folding and improve stability as well as serving regulatory functions. (wikipedia.org)
  • Three different protein prenyltransferases (farnesyltransferase and geranylgeranyltransferases I and II) catalyze the attachment of prenyl lipid anchors 15 or 20 carbons long to the carboxyl termini of a variety of eukaryotic proteins. (biomedcentral.com)
  • The chromosomal locations and number of exons from protein prenyltransferase genes in the major eukaryotic model organisms are shown in Table 2 . (biomedcentral.com)
  • amide bond formation amino acid addition arginylation, a tRNA-mediation addition polyglutamylation, covalent linkage of glutamic acid residues to the N-terminus of tubulin and some other proteins. (wikipedia.org)
  • Proteins are created by ribosomes translating mRNA into polypeptide chains, which may then change to form the mature protein product. (wikipedia.org)
  • In the actual research, initial involving HIF-1 by hypoxia and dimethyloxaloylglycine (DMOG), any hypoxia mimic, decreased Ref-1 mRNA and also protein appearance in man microvascular endothelial tissue (HMEC-1). (notes.io)
  • In the same way, adenoviral receiving the settled down type of HIF-1 alpha diminished Ref-1 mRNA as well as proteins amounts. (notes.io)
  • O-acylation (esters), N-acylation (amides), S-acylation (thioesters) acetylation, the addition of an acetyl group, either at the N-terminus of the protein or at lysine residues. (wikipedia.org)
  • These proteins share a core structure, the conserved G-box (GDP/GTP) binding domain, of approximately 170 residues [ 3 ]. (oncotarget.com)
  • There are three different protein prenyltransferases in humans: farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) share the same motif (the CaaX box) around the cysteine in their substrates, and are thus called CaaX prenyltransferases, whereas geranylgeranyltransferase 2 (GGT2, also called Rab geranylgeranyltransferase) recognizes a different motif and is thus called a non-CaaX prenyltransferase [ 1 ]. (biomedcentral.com)
  • The genomic organization of the human genes that encode protein prenyltransferases is shown in Figure 1 . (biomedcentral.com)
  • (b) genes encoding non-CaaX protein prenyltransferases are much shorter. (biomedcentral.com)
  • 1996) Protein prenyltransferases. (guidetopharmacology.org)
  • Attachment of lipid molecules, known as lipidation, often targets a protein or part of a protein attached to the cell membrane. (wikipedia.org)
  • 2001) Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. (guidetopharmacology.org)
  • 1995) Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release. (guidetopharmacology.org)
  • Gene structures and chromosomal locations of human protein prenyltransferase subunit genes. (biomedcentral.com)
  • 1994) Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. (guidetopharmacology.org)
  • biotinylation: covalent attachment of a biotin moiety using a biotinylation reagent, typically for the purpose of labeling a protein. (wikipedia.org)
  • In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. (novusbio.com)
  • Automatic comparisons of data from expressed sequence tags (ESTs) with genes (for example using the program Acembly, for which the results are available from the NCBI AceView server [ 2 ]) shows that all the human protein prenyltransferase genes have multiple alternative splice variants. (biomedcentral.com)
  • Changes in the level of prenylated proteins may serve a critical function in a variety of diseases. (umn.edu)
  • spontaneous isopeptide bond formation, as found in many surface proteins of Gram-positive bacteria. (wikipedia.org)
  • These findings implicate the potential role of PCAIs as anticancer agents through their direct interaction with monomeric G-proteins. (oncotarget.com)
  • Gao S, Yu R, Zhou X. (2016) The Role of Geranylgeranyltransferase I-Mediated Protein Prenylation in the Brain. (guidetopharmacology.org)
  • This study tested this hypothesis by determining the effect of the PCAIs on the levels of RAS and related monomeric G-proteins. (oncotarget.com)
  • Metabolic labeling using modified isoprenoid probes followed by enrichment and proteomic analysis allows the identities and levels of prenylated proteins to be investigated. (umn.edu)
  • glycation, the addition of a sugar molecule to a protein without the controlling action of an enzyme. (wikipedia.org)
  • Prenylation creates a hydrophobic domain on protein tails which acts as a membrane anchor. (guidetopharmacology.org)
  • Finding effective therapies against cancers driven by mutant and/or overexpressed hyperactive G-proteins remains an area of active research. (oncotarget.com)
  • Carbonylation is one example that targets the modified protein for degradation and can result in the formation of protein aggregates. (wikipedia.org)
  • In relation to the causative association between oncogenic Ras proteins and cancer, farnesyltransferase has become an important mechanistic drug discovery target. (guidetopharmacology.org)