• phosphatidylinositol 3-kina
  • Although different tumor types rely to differing degrees on activation of the Raf, phosphatidylinositol 3-kinase, and Ral guanine nucleotide exchange factor effector pathways ( 5 ), the particular importance of Raf activation has long been appreciated ( 6 ). (aacrjournals.org)
  • In one approach, a single signaling pathway is "vertically" targeted, with drugs inhibiting multiple steps in a signaling cascade: For example, pretreatment of A549 lung carcinoma cells with the phosphatidylinositol 3-kinase inhibitor PX-866, which strongly potentiates the action of the epidermal growth factor receptor inhibitor Iressa ( 9 ). (aacrjournals.org)
  • downstream
  • Similarly to caspase-8, active caspase-9 then proteolytically activates downstream effector caspases, which by degrading various cellular proteins propagate the apoptotic signal. (bloodjournal.org)
  • The protein kinase C inhibitor bis(indolyl)maleimide inhibitor BIM1 is clearly seen in the structure of PKCiota (residue 574-turn motif), need to be phosphorylated towards a PKCbeta-specific inhibitor site-directed mutagenesis of the compound for its full activation and co-crystallized as an asymmetric pair which is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) are downstream characteristics of PKCs and PKB/AKT. (wikipedia.org)
  • The beta chain contains the intracellular tyrosine kinase domain and a tail on the C-terminal which is vital for the docking of substrates and downstream signalling. (wikipedia.org)
  • Phosphorylation occurs in tyrosines close to the C-terminus, creating a multi-functional docking site which recruits adaptor proteins and leads to downstream signalling. (wikipedia.org)
  • Following MET activation, transphosphorylation occurs on Tyr 1234 and Tyr 1235 C-terminal region contains two crucial tyrosines (Tyr 1349 and Tyr 1356), which are inserted into the multisubstrate docking site, capable of recruiting downstream adapter proteins with Src homology-2 (SH2) domains. (wikipedia.org)
  • pathways
  • Among these different pathways, Ras interaction with and activation of Raf serine/threonine kinases (Raf-1, A-Raf, and B-Raf), phosphatidylinositol 3-kinases, and Ral guanine nucleotide exchange factors has been shown to be critical for tumor promotion. (aacrjournals.org)
  • We identified distinct phosphatidylinositol 3-OH kinase (PI3K)-linked pathways supporting basal and insulin-triggered NE transport in the human noradrenergic neuroblastoma, SK-N-SH. (aspetjournals.org)
  • Thus, in lymphocytes, as in other cell types, glycolipid-based domains provide sites of integration of signaling pathways involved in GPI-anchored protein endocytosis. (rupress.org)
  • endocytosis
  • Both proteins localize to actin patches, which in budding yeast are involved in endocytosis (actin may provide an assembly force that overcomes the osmotic forces of turgor pressure). (rupress.org)
  • Both Pan1p and the similar mammalian protein Eps15 have been implicated in endocytosis, which brings up the controversial question of whether actin is involved in mammalian endocytosis. (rupress.org)
  • The more immediate question of how all the actin-patch proteins cooperate in yeast endocytosis will probably have to wait for the development of an in vitro endocytosis assay. (rupress.org)
  • Endocytosis of GPI-anchored proteins in human lymphocytes: role of glycolipid-based domains, actin cytoskeleton, and protein kinases. (rupress.org)
  • They cluster into glycolipid-based membrane domains and caveolae, plasmalemmal vesicles involved in the transcytosis and endocytosis of these surface proteins. (rupress.org)
  • Staurosporine, by inhibiting mobility within the terminal, may favor recapture of new vesicles near sites of endocytosis. (jneurosci.org)
  • amino acid
  • the amino acid composition of this pocket is unique to Src family kinases. (ebi.ac.uk)
  • The biosynthesis of staurosporine starts with the amino acid L-tryptophan in its zwitterionic form. (wikipedia.org)
  • The HSulf1 gene (GenBank accession number AY101175) has an open reading frame of 2616 bp, encoding a protein of 871 amino acid (aa), and HSulf2 (GenBank accession number AY101176) has an open reading frame of 2613 bp, encoding a protein of 870 aa. (wikipedia.org)
  • MET is transcribed into a 6,641 bp mature mRNA, which is then translated into a 1,390 amino-acid MET protein. (wikipedia.org)
  • inhibit
  • The MCP compounds were identified as inhibitors of Ras-Raf interactions and previously shown to inhibit multiple Ras-dependent transformation phenotypes when used as monoagents in cell culture analyses. (aacrjournals.org)
  • Two of the more important ones to date have been Arcyriacyanin A, which was found to inhibit a panel of human cancer cells by effecting PKC and protein tyrosine kinase, and lycogalic acid dimethyl ester A (found in Tokushima, Japan from Lycogala epidendrum), which showed strong antiviral activity. (wikipedia.org)
  • Balanol was originally discovered to inhibit PKC and many of its isoforms in humans (α, β-Ι, β-ΙΙ, γ, δ, ε, η), with an inhibition profile similar to that of staurosporine. (wikipedia.org)
  • effector
  • Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. (wikipedia.org)
  • Effector proteins are usually critical for virulence. (wikipedia.org)
  • Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a novel membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface. (wikipedia.org)
  • More importantly, it is difficult to prove experimentally that a predicted effector is actually secreted into a host cell because the amount of each effector protein is tiny. (wikipedia.org)
  • Yersinia inhibits phagocytosis through the concerted actions of several effector proteins, including YopE which acts as a RhoGAP and inhibits Rac-dependent actin polymerization. (wikipedia.org)
  • catalytic activity
  • Protein kinases are also found in bacteria and plants, and include the pseudokinase sub-family, which exhibit unusual features including atypical nucleotide binding and weak, or no, catalytic activity and are part of a much larger pseudoenzyme group of 'degraded' enzyme relatives that are found throughout life, where they take an active participation in mechanistic cellular signaling. (wikipedia.org)
  • subunit
  • Association of two components of this putative landmark provides a link from pheromone signaling to the cytoskeleton: the β subunit of a heterotrimeric G protein is involved in pheromone detection, and the guanine nucleotide exchange factor Cdc24p helps to orient and recruit the actin cytoskeleton. (rupress.org)
  • activation
  • Role of guanine nucleotide-binding protein and tyrosine kinase in platelet-activating factor activation of phospholipase C in A431 cells: proposal for dual mechanisms. (aspetjournals.org)
  • Based on these observations the involvement of PT-sensitive and -insensitive guanine nucleotide-binding protein(s) (G-protein) as well as the role of tyrosine kinase in the activation of PLC by PAF was considered further. (aspetjournals.org)
  • In alpha-toxin permeabilized cells, PT blocked GTP-gamma-S potentiation of PLC activation by PAF, thus suggesting that PT-insensitive G-proteins were not involved in PAF activation of PLC in A431 cells. (aspetjournals.org)
  • The protective effect of TPA on CYP2E1-dependent AA + Fe toxicity seemed to involve a PKC-related survival mechanism, since PKC inhibitors such as Ro 31-8425 (bisindolylmaleimide X hydrochloride) or staurosporine abolished that protection, and activation of PKC by TPA was an early event that occurs prior to the developing toxicity. (aspetjournals.org)
  • Where Thr-412 (activation loop of the kinase domain) at PKCiota/lambda phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that sort cargo to the anterograde pathway the phosphorylation pathway(s) involved in this phenomenon mimic glutamate and can adopt two limiting diastereomeric (syn and anti) conformation biosynthetically related indolocarbazole analogs and in Proto-oncogene serine/threonine-protein kinase Pim-1-Peptide as a phosphorylation target including itself. (wikipedia.org)
  • therapeutic
  • An important clinical task is to coherently integrate the use of protein-targeted drugs into preexisting therapeutic regimens, with the goal of improving treatment efficacy. (aacrjournals.org)
  • These inhibitors may have therapeutic application in the treatment of various types of cancers. (wikipedia.org)
  • conformation
  • The bound BIM1 inhibitor blocks the ATP-binding site and puts the kinase domain into an intermediate open conformation. (wikipedia.org)
  • The StaN enzyme reorients the sugar by attaching it to the 2nd indole nitrogen into an unfavored conformation to form intermediated O-demethyl-N-demethyl-staurosporine. (wikipedia.org)
  • Activity of MAP kinases is restricted by a number of protein phosphatases, which remove the phosphate groups that are added to specific serine or threonine residues of the kinase and are required to maintain the kinase in an active conformation. (wikipedia.org)
  • heat shock pr
  • While Hsc70 also performed chaperone functions under normal conditions, unlike canonical heat shock proteins, Hsc70 is constitutively expressed and performs functions related to normal cellular processes, such as protein ubiquitylation and degradation. (wikipedia.org)
  • In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. (wikipedia.org)
  • basal
  • In Chop −/− macrophages, the increase in Ero1a mRNA and both basal and ER stress-induced ERO1-α protein were diminished. (rupress.org)
  • actin
  • Many proteins bind actin, and many other proteins bind actin-binding proteins. (rupress.org)
  • isolate actin-regulating kinase 1 (Ark1p) based on its two-hybrid interaction with the actin-binding protein Sla2p. (rupress.org)
  • Deletion of one kinase gene causes only a slight slowing of growth, but deletion of both genes yields cells that die at extreme temperatures and grow very slowly at 30°C. Most of the surviving cells are enlarged and have huge clumps of filamentous actin in the cytoplasm. (rupress.org)
  • This process, which is regulated by both protein kinase C and A activity, is tightly controlled by the dynamic organization of actin cytoskeleton, and may be critical for polarized contacts of circulating cells. (rupress.org)
  • interaction
  • MRI, immunoblot and immunofluorescence tools has allowed researchers to identify and observe tau protein aggregation both intra and intercellullary as well as their interaction with other proteins. (wikipedia.org)
  • Region of homology to semaphorins (Sema domain), which includes the full α-chain and the N-terminal part of the β-chain Cysteine-rich MET-related sequence (MRS domain) Glycine-proline-rich repeats (G-P repeats) Four immunoglobulin-like structures (Ig domains), a typical protein-protein interaction region. (wikipedia.org)
  • activity
  • Protein kinase C activity is required for normal cell wall synthesis. (rupress.org)
  • PAF stimulated tyrosine kinase activity as observed with the increase in radioactivity associated with proteins immunoprecipitated with polyclonal antibodies to phosphotyrosine residues. (aspetjournals.org)
  • When encapsulated in liposome nanoparticle, staurosporine is shown to suppress tumors in vivo in a mouse model without the toxic side effects which have prohibited its use as an anti-cancer drug with high apoptotic activity. (wikipedia.org)
  • The chemical activity of a kinase involves transferring a phosphate group from a nucleoside triphosphate (usually ATP) and covalently attaching it to specific amino acids with a free hydroxyl group. (wikipedia.org)
  • Because protein kinases have profound effects on a cell, their activity is highly regulated. (wikipedia.org)
  • Activity of these protein kinases can be regulated by specific events (e.g. (wikipedia.org)
  • Two major factors influence activity of MAP kinases: a) signals that activate transmembrane receptors (either natural ligands or crosslinking agents) and proteins associated with them (mutations that simulate active state) b) signals that inactivate the phosphatases that restrict a given MAP kinase. (wikipedia.org)
  • Over the course of the next decade, further study of the compound showed some fungi inhibition, hypotensive activity, and most importantly, a broad protein kinase inhibitor. (wikipedia.org)
  • SU-11274 was evolved by substitution at the 5-position of the indolinone and by adding a 3,5-dimethyl pyrrole group, PHA-665752 was evolved - a second-generation inhibitor with better potency and activity. (wikipedia.org)
  • The protein possesses tyrosine kinase activity. (wikipedia.org)
  • inhibits
  • Staurosporine, which at hippocampal synapses partially inhibits unloading of FM1-43, but does not block uptake of antibody probes, prevents this intermixing. (jneurosci.org)
  • bacteria
  • His laboratory produced the first evidence for quorum sensing in bacteria, early evidence of the molecular mechanisms of circadian clock regulation in organisms (first using dinoflagellate luminescence and then expanded to other cellular proteins), and some of the initial studies of energy transfer in green fluorescent proteins (GFP) in cnidarian luminescence. (wikipedia.org)
  • Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). (wikipedia.org)
  • gene
  • PART has been associated with Microtubule association tau protein (MAPT) H1 haplotype and no association has been seen with APOE ε4, a gene strongly linked to AD. (wikipedia.org)
  • Transformatation in tau gene on chromosome 17 can be linked to PART due to the fact that the tau protein analyzed from PART NFTs consist fo 3R and 4R isoforms. (wikipedia.org)
  • MAPT gene results in different tau protein isoforms due to splicing patterns of exon 10. (wikipedia.org)
  • Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene on chromosome 11. (wikipedia.org)
  • This gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 (Hsp70) family. (wikipedia.org)
  • Heat shock 70 kDa protein 1, also termed Hsp72, is a protein that in humans is encoded by the HSPA1A gene. (wikipedia.org)
  • The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. (wikipedia.org)
  • potency
  • The potency of staurosporine against Lck derives in part from an induced movement of the glycine-rich loop of the enzyme upon binding of this ligand, which maximizes the van der Waals interactions present in the complex. (ebi.ac.uk)
  • Tumor
  • Phorbol esters activate protein kinase C (PKC), thereby blocking cell differentiation and promoting tumor growth. (aspetjournals.org)
  • When injected into the mouse glioblastoma model, staurosporine is found to accumulate primarily in the tumor via fluorescence confirmation, and the mice did not suffer weight loss compared to the control mice administered with the free compound, an indicator of reduced toxicity. (wikipedia.org)
  • Furthermore, this protein enhances antigen-specific tumor immunity by facilitating more efficient antigen presentation to cytotoxic T cells. (wikipedia.org)
  • indolocarbazole
  • The value of such calculations lies in understanding a variant was designed which showed improved binding characteristics of configurationally stable atropisomeric bisindolylmaleimides where the two kinase domains, and two different inhibitor conformers bind in different orientations, the hinge region of staurosporine-Pim-1 resembles co-crystallized as an asymmetric pair of biosynthetically 'related' indolocarbazole analogs. (wikipedia.org)
  • Staurosporine is an indolocarbazole. (wikipedia.org)