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  • phosphorylation
  • 7. These results demonstrate that PTK-mediated phosphorylation events are important for the regulation of adhesion molecule expression by human endothelial cells, and additionally show that PTK inhibitors differentially affect upregulation of different adhesion molecules, implicating divergent regulatory pathways for cytokine-induced adhesion molecule expression. (mysciencework.com)
  • A growing body of experimental evidence accumulated over the last several years indicates that the activity of L-type Ca 2+ channels can be directly regulated by protein tyrosine kinase (PTK)-dependent phosphorylation. (aspetjournals.org)
  • that insulin-like growth factor-1 (IGF-1) potentiates the L-type Ca 2+ current in cultured cerebellar granule neurons through Src-mediated phosphorylation of a specific tyrosine residue (Tyr 2122 ) near the C terminus of the α 1 subunit of the neuronal Ca v 1.2 channel. (aspetjournals.org)
  • citation needed] Phosphorylation regulates many biological processes, and protein kinase inhibitors can be used to treat diseases due to hyperactive protein kinases (including mutant or overexpressed kinases in cancer) or to modulate cell functions to overcome other disease drivers. (wikipedia.org)
  • They are also called tyrphostins, the short name for "tyrosine phosphorylation inhibitor", originally coined in a 1988 publication, which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR). (wikipedia.org)
  • potent
  • SMARCB1 is a core protein subunit of the 15 subunit SWI/SNF (or BAF) complex involved in regulating the nucleosome architecture of our genome and has been shown to be a potent tumor suppressor gene, meaning that its primary role is to control cell division and to even halt division under appropriate circumstances (i.e. signals to over-replicate). (wikipedia.org)
  • receptors
  • Currently there are several drugs launched or in development that target protein kinases and the receptors that activate them: Note: AD = Approval date. (wikipedia.org)
  • This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. (wikipedia.org)
  • Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. (wikipedia.org)
  • Cytokines including interleukins, interferons and hemopoietins activate the Janus kinases, which associate with their cognate receptors. (wikipedia.org)
  • Vascular inflammation can be caused by upregulation of Ang-II, which is produced locally by inflamed vessels and induces synthesis and secretion of IL-6, a cytokine responsible for induction of angiotensinogen synthesis in liver through JAK/STAT3 pathway, which gets activated through high affinity membrane protein receptors on target cells, termed IL-6R-chain recruiting gp-130 that is associated with tyrosine kinases (Jaks 1/2, and Tyk2 kinase). (wikipedia.org)
  • gene
  • ETV6 (i.e. translocation-Ets-leukemia virus) protein is a transcription factor that in humans is encoded by the ETV6 (previously known as TEL) gene. (wikipedia.org)
  • Two unrelated kindreds were found to have autosomal dominant inherited mutations in the ETV6 gene, one family with a germline DNA substitution termed L349P that lead to replacing leucine with proline at amino acid 349 in the DNA binding domain of the ETV6, the second, termed N385fs, in germline DNA caused the lose of five base pairs ETV6 and a truncated ETV6 protein. (wikipedia.org)
  • This gene encodes a member of the tyrosine kinase and, to be more specific, the Janus kinases (JAKs) protein families. (wikipedia.org)
  • A mutation in this gene has been associated with hyperimmunoglobulin E syndrome (HIES) - a primary immunodeficiency characterized by elevated serum immunoglobulin E. Tyrosine kinase 2 has been shown to interact with FYN, PTPN6, IFNAR1, Ku80 and GNB2L1. (wikipedia.org)
  • Bcr-Abl was regarded as highly attractive target for drug intervention since the Bcr-Abl fusion gene encodes a constitutively activated kinase. (wikipedia.org)
  • regulates
  • The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. (wikipedia.org)
  • conformation
  • The Lyn kinase domain was determined in its "active" conformation, but in the unphospho-rylated state. (edu.au)
  • Since then crystallographic studies have revealed that imatinib binds to the kinase domain of Abl only when the domain adopts the inactive or "closed" conformation. (wikipedia.org)
  • Initially
  • SU6656 was initially identified as a Src kinase inhibitor by virtue of its ability to reverse an effect that an activated mutant form of Src (hu SRC Y530F) has on the actin cytoskeleton, namely the formation of podosome rosettes, otherwise known as invadopodia. (wikipedia.org)
  • BIOLOGY
  • While drug screening was used to develop imatinib, second generation TKI's were developed with rational drug design approach due to increased knowledge in structural biology of the Bcr-Abl tyrosine kinase. (wikipedia.org)
  • drug
  • Development of a Tyk2 inhibitor appears to be a rational approach in the drug discovery. (wikipedia.org)
  • Drug discovery that specifically targeted the ATP binding site of a single kinase was regarded as quite a challenging task since hundreds of protein kinases were known in the human genome. (wikipedia.org)
  • Imatinib (Gleevec) was discovered in 1992 and is regarded as first generation drug since it is the first Bcr-Abl tyrosine kinase inhibitor to be used in the treatment of CML. (wikipedia.org)
  • Sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar), is a kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma), advanced primary liver cancer (hepatocellular carcinoma), and radioactive iodine resistant advanced thyroid carcinoma. (wikipedia.org)
  • cells
  • Effects of protein tyrosine kinase inhibitors on cytokine-induced adhesion molecule expression by human umbilical vein endothelial cells. (mysciencework.com)
  • Here, we demonstrate that cotreatment with JQ1 and the FLT3 tyrosine kinase inhibitor (TKI) ponatinib or AC220 synergistically induce apoptosis of cultured and primary CD34 + human AML blast progenitor cells (BPC) expressing FLT3-ITD. (aacrjournals.org)
  • Furthermore, cotreatment with JQ1 and the pan-histone deacetylase inhibitor (HDI) panobinostat synergistically induced apoptosis of FLT3-TKI-resistant MOLM13-TKIR and MV4-11-TKIR cells. (aacrjournals.org)
  • Cells were harvested 18 h after transfection and lysed at 4 C in a Dounce homogenizer in 250 mm sucrose, 20 mm TrisHCl, 1 mm CaCl2, 1 mm MgCl2, cOmplete protease inhibitor cocktail (Roche Applied Science), pH 8. (molecularcircuit.com)
  • Resistance
  • Even though the first Bcr-Abl TK inhibitor was named "the magic bullet" to cure cancer by TIME magazine, a second generation of Bcr-Abl TKI was subsequently developed to combat the initial resistance that emerged. (wikipedia.org)
  • activation
  • Signalling through IL-4/IL-13 complexes is thought to occur through IL-4Rα-chain, which is responsible for activation of JAK-1 and Tyk2 kinases. (wikipedia.org)
  • The shift of the AspPheGly triad at the N-terminal end of the activation loop results in the exposure of a binding pocket which can be utilized by inhibitors. (wikipedia.org)
  • induces
  • This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. (wikipedia.org)
  • TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a consequence, act to halt the cell cycle and stop proliferation. (wikipedia.org)
  • interacts
  • this MKB/KIM motif of DUSP interacts with the common domain of MAP kinases to mediate the enzyme-substrate interaction [ 1 ]. (scitechnol.com)
  • When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 domain interact with the flexible linker domain and thereby keeps the inactive unit tightly bound. (wikipedia.org)
  • Chem
  • J Am Chem Soc 127:4625-4631 Martin E, Berka V, Bogatenkova E, Murad F, Tsai A L (2006) Ligand selectivity of soluble guanylyl cyclase - effect of the hydrogen-bonding tyrosine in the distal heme pocket on binding of oxygen, nitric oxide, and carbon monoxide. (alusdomundo.com)
  • embryonic development
  • In contrast, the knockout of the FYVE domain-containing enzymes in A. thaliana, D. melanogaster, C. elegans and M. musculus leads to embryonic lethality indicating that the FYVE-domain-containing phosphoinositide kinases have become essential in embryonic development of multicellular organisms. (wikipedia.org)
  • In higher eukaryotes, the enzymes acquire one additional domain, a role in the production of PtdIns5P, a new set of interacting proteins and become essential in embryonic development. (wikipedia.org)
  • mediate
  • Src contains at least three flexible protein domains, which, in conjunction with myristoylation, can mediate attachment to membranes and determine subcellular localization. (wikipedia.org)
  • functional
  • Additionally, the functional interaction between the H-NOX and kinase was mediated by NO (Price et al. (alusdomundo.com)
  • PIKfyve is a large protein, containing a number of functional domains and expressed in several spliced forms. (wikipedia.org)
  • amino acids
  • Apart from the "leucine zipper" and the "basic region" which are important for dimerization and DNA-binding, the c-jun protein contains three short regions, which consist of clusters of negatively charged amino acids in its N-terminal half that are important for transcriptional activation in vivo. (wikipedia.org)
  • Δ324 found at low levels in human and mouse cells - an alternative splice variant encoding an 88kDa protein lacking zinc fingers 6 and 7 Δ105 variant is unique to mice, and results in a protein truncated by 105 amino acids at the acidic C-terminus. (wikipedia.org)
  • molecules
  • IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. (wikipedia.org)
  • The BCR-ABL protein can be inhibited by various small molecules. (wikipedia.org)
  • regulation
  • Thus, the activation of the HBP by nutrients represents a biochemical link between nutrient availability, mitochondrial proteins, and energy expenditure, and it is likely to play an important role in the regulation of energy balance. (jci.org)
  • domain
  • In support of this hypothesis, an H-NOX domain and a predicted histidine kinase from Shewanella oneidensis were isolated and found to interact in vitro. (alusdomundo.com)
  • c-Src includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. (wikipedia.org)
  • By directly binding membrane PtdIns(3)P, the FYVE finger domain of PIKfyve is essential in localizing the protein to the cytosolic leaflet of endosomes. (wikipedia.org)
  • Single copy genes, encoding similarly-structured FYVE-domain-containing phosphoinositide kinases exist in most genomes from yeast to man. (wikipedia.org)
  • The MECOM protein contains 2 domains characterized by 7 zinc finger motifs followed by a proline-rich transcription repression domain, 3 more zinc finger motifs and an acidic C-terminus. (wikipedia.org)
  • tumor
  • Interferons (IFNs) are a group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells. (wikipedia.org)
  • known
  • In addition, interferons induce production of hundreds of other proteins-known collectively as interferon-stimulated genes (ISGs)-that have roles in combating viruses and other actions produced by interferon. (wikipedia.org)
  • Genetic
  • Genetic combinatorial marking using lentiviral vectors encoding fluorescent proteins (FPs) enabled cell fate mapping through advanced microscopy imaging. (jove.com)
  • thus
  • We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. (jci.org)
  • expression
  • Conversely, the expression of uncoupling protein-1 and of the same mitochondrial genes was increased in brown adipose tissue. (jci.org)