• In recent years, the search for intracellular signaling integrator downstream of receptor tyrosine kinases provided valuable novel substrates. (springer.com)
  • The class 1A phosphoinositide 3-kinase (PI3K) beta (PI3Kβ) is functionally unique in the ability to integrate signals derived from receptor tyrosine kinases (RTKs), heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs), and Rho-family GTPases. (elifesciences.org)
  • The ALK gene provides instructions for making a protein called ALK receptor tyrosine kinase, which is part of a family of proteins called receptor tyrosine kinases (RTKs). (medlineplus.gov)
  • Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. (medlineplus.gov)
  • Acetyl-L-carnitine ameliorates spatial memory deficits induced by inhibition of phosphoinositol-3 kinase and protein kinase C". Journal of Neurochemistry. (wikipedia.org)
  • This study was designed to examine potential in vivo mechanisms of AMP-activated protein kinase (AMPK) phosphorylation inhibition and its downstream signaling consequences during the recovery period after a single bout of sprint exercise. (ulpgc.es)
  • 1 nM IC 50 ) to inhibition of two cell cycle-regulating proteins, polo-like kinase 1 and Aurora kinase A. Finally, we show that two of these cell lines, CUTO32 and CUTO42, successfully establish xenografted tumors in nude mice. (nih.gov)
  • SIGNIFICANCE STATEMENT: We have derived and characterized three novel rearranged during transfection (RET) fusion non-small cell lung cancer cell lines and demonstrated that they have differential responses to RET inhibition as well as regulation of downstream signaling, an area that has previously been limited by a lack of diverse cell line modes with endogenous RET fusions. (nih.gov)
  • Morphological rescue is possible following Rho kinase inhibition in an oligodendrocyte subset. (jneurosci.org)
  • Inhibition of the kinase domain is halted through binding of the Ras-binding domain, or residues 155-227 of the protein, to the Ras-GTP effector domain. (news-medical.net)
  • In a series of experiments in mice, researchers found that inhibition of the kinase CaMKII -- or even some of its downstream components -- lowered blood glucose and insulin levels, Ira Tabas, MD, PhD , of Columbia University Medical Center in New York City, and colleagues reported online in Cell Metabolism . (medpagetoday.com)
  • In the current study, they found CaMKII inhibition suppresses levels of the pseudo-kinase TRB3 to improve Akt-phosphorylation, thereby improving insulin sensitivity. (medpagetoday.com)
  • Rearranged during transfection ( RET ) rearrangements occur in 1% to 2% of lung adenocarcinomas as well as other malignancies and are now established targets for tyrosine kinase inhibitors. (nih.gov)
  • These data highlight the utility of new RET+ models to elucidate differences in response to tyrosine kinase inhibitors and downstream signaling regulation. (nih.gov)
  • These data offer important insight into regulation of response to RET tyrosine kinase inhibitors and other potential therapeutic targets. (nih.gov)
  • Whereas the standard immunosuppressive agents foster development of PTLDs, the impact of novel immunosuppressive agents from the group of selective inhibitors of TOR serine/treonine kinase such as rapamycin and its derivatives including RAD remains undetermined. (upenn.edu)
  • Indeed, we observed partial restoration of dexamethasone sensitivity with a combination of dexamethasone and inhibitors targeting either these kinases or β-catenin. (lu.se)
  • Wortmannin, a steroid metabolite of the fungi Penicillium funiculosum, Talaromyces wortmannii, is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). (wikipedia.org)
  • One of these, sonolisib (PX-866), has been shown to be an irreversible inhibitor of PI-3 kinase with efficacy when delivered orally. (wikipedia.org)
  • VEGF-induced pMF was attenuated by the MEK/ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis( o -aminophenylmercapto)butadiene] and was abolished by the phosphotidinositol 3 kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4 H )-benzopyran-4-one hydrochloride], demonstrating that ERK mitogen-activated protein kinases and Akt are both required for full expression of VEGF-induced pMF. (jneurosci.org)
  • Acanthamoeba -mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. (asm.org)
  • Bosutinib is an oral, once-daily, kinase inhibitor, which limits cancer cell growth by inhibiting the Abl and Src signaling pathways. (aol.com)
  • Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma. (lu.se)
  • We investigated the role of phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), a key upstream factor of PI3K/AKT, and the therapeutic effect of PIP5Kα inhibitor on subtypes of BC. (lu.se)
  • It displays a similar potency in vitro for the class I, II, and III PI3K members although it can also inhibit other PI3K-related enzymes such as mTOR, DNA-PKcs, some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high concentrations Wortmannin has also been reported to inhibit members of the polo-like kinase family with IC50 in the same range as for PI3K. (wikipedia.org)
  • small GTPase Rho A and its own downstream effector Rho kinase have already been shown to play an important role in the regulation of vascular easy muscle contraction (2 22 28 Clean muscle contraction is mediated by the phosphorylation of myosin light chains and the extent of myosin light chain phosphorylation is regulated by the opposing activities of myosin light chain kinase and phosphatase. (academicediting.org)
  • We discovered that our RET + cell lines had differential regulation of the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B (AKT) pathways. (nih.gov)
  • Our analysis indicated that ligand affinity differentially affected signaling pathways associated with specific kinases and biological processes. (nature.com)
  • They indicate that pathways involving STAT3, PI3K/AKT and, apparently, STAT5 are constitutively activated by this kinase. (upenn.edu)
  • Induction of canonical autophagy is mainly controlled by the AKT/mTOR and AMPK signaling pathways and relies on the activation and assembly of two macromolecular complexes, the ATG1/ULK1 and the Class III phosphatidylinositol 3-kinase (PI3K) complex (Figure 1 ) [ 5 ]. (hindawi.com)
  • In addition, they play important roles in gene transcription (via activation of mitogen activated protein (MAP) kinase pathways and, in higher eukaryotes, the transcription factor NFκB), generation of reactive oxygen species, apoptosis, and cell-cycle progression. (biomedcentral.com)
  • In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. (bvsalud.org)
  • Further mechanistic studies revealed that these functions were controlled by the eukaryotic initiation factor (eIF) 4E and the mitogen-activated protein kinase (MAPK) interacting protein kinase (MNK) signaling pathways, which regulate which mRNAs will be translated. (lu.se)
  • Phosphoinositide-3-kinase (PI3K) activates an important cell survival signaling pathway, and constitutive activation is seen in ovarian, head and neck, urinary tract, cervical and small cell lung cancer. (wikipedia.org)
  • Phosphoinositide 3-kinase (PI3K) plays a vital role in plant response to abiotic stress. (frontiersin.org)
  • Phosphoinositide 3-kinase (PI3K) as a key regulator of lipid signal has been reported to be involved in autophagy. (frontiersin.org)
  • Phosphoinositide 3-kinase (PI3K) signaling contributes to a variety of processes, mediating many aspects of cellular function, including nutrient uptake, anabolic reactions, cell growth, proliferation, and survival. (mdpi.com)
  • Previous experiments have not been able to elucidate whether interactions with membrane-tethered proteins primarily control PI3Kβ localization versus directly modulate lipid kinase activity. (elifesciences.org)
  • To address this gap in our understanding of PI3Kβ regulation, we established an assay to directly visualize and decipher how three binding interactions regulate PI3Kβ when presented to the kinase in a biologically relevant configuration on supported lipid bilayers. (elifesciences.org)
  • Using single molecule Total Internal Reflection Fluorescence (TIRF) Microscopy, we determined the mechanism controlling membrane localization of PI3Kβ, prioritization of signaling inputs, and lipid kinase activation. (elifesciences.org)
  • Although pY peptides strongly localize PI3Kβ to membranes, they only modestly stimulate lipid kinase activity. (elifesciences.org)
  • Signaling intensification through epithelial growth factor receptor (EGFR), mitogenactivated protein kinase (MAPK) pathway, Phosphatidylinositol 3-kinase (PI3K) pathway and overactivation of the translation initiation complex (TIC) has been previously characterized in RCC cell lines and tumor samples. (usp.br)
  • Glioblastoma (GBM), a very aggressive and incurable tumor, often results from constitutive activation of EGFR (epidermal growth factor receptor) and of phosphoinositide 3-kinase (PI3K). (sdbonline.org)
  • Epidermal growth factor receptor phosphorylation and downstream signaling by an aqueous extract of hog barn dust in airway epithelial cells. (cdc.gov)
  • Thus we hypothesized that HDE would lead to EGFR phosphorylation and downstream activation of ERK/MAPK signaling. (cdc.gov)
  • This gene encodes a receptor tyrosine kinase. (nih.gov)
  • 4 It encodes a receptor tyrosine kinase involved in the development and homeostasis of several cell lines including melanocytic (pigment), hematologic (blood), mast, and germ cells. (creation.com)
  • Mammalian STE20-like kinase MST4 regulates multiple cellular aspects such as cell polarity and proliferation. (rcsb.org)
  • PAK, a kinase that regulates the actin cytoskeleton downstream of Rac, also binds FMRP. (fraxa.org)
  • Binding of SH2 domains to their in vivo targets recruits the SH2 domain-containing protein to its proper signalling complex and thereby initiates or regulates downstream signalling cascades (reviewed in Schlessinger and Lemmon, 2003). (lu.se)
  • The improvements also occurred when they knocked out downstream processes, including p38 and MAPK-activating protein kinase 2 (MK2). (medpagetoday.com)
  • En los mamíferos, existen varias vías de MAPK diferentes, como la vía de ERK (cinasa regulada por señales extracelulares), la vía de SAPK/JNK (proteína-cinasa activada por el estrés/cinasa c-jun) y la vía de la cinasa p38. (bvsalud.org)
  • The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. (nih.gov)
  • The receptor makes a single pass through the cell membrane and contains an intracellular kinase catalytic region divided by a hydrophilic insert. (creation.com)
  • These reagents led to rapid clearance of VEGFR-2 from the cell surface without kinase activation, followed by an increase in intracellular receptor-positive vesicles, suggesting receptor internalization. (open.ac.uk)
  • An intracellular signaling system involving the mitogen-activated protein kinase cascades (three-membered protein kinase cascades). (bvsalud.org)
  • The MAPKs then act on various downstream targets to affect gene expression. (bvsalud.org)
  • We observed that dexamethasone exposure caused upregulation of Aurora kinase and its various downstream effector kinases such as JAK, p38, mTOR, and S6K. (lu.se)
  • Prolonged hypoxia promotes the activation of RIPK1 kinase by modulating its proline hydroxylation, independent of the TNFα-TNFR1 pathway. (nature.com)
  • These mutations impaired MST4 kinase activation and function within the cell. (rcsb.org)
  • Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse. (rupress.org)
  • One is in the activation segment of the kinase domain. (news-medical.net)
  • In order to become active, the CR3 kinase domain must be converted to its active form by phosphorylation of the activation loop. (news-medical.net)
  • Downstream signaling is triggered by receptor dimerization, kinase activation, and receptor internalization. (open.ac.uk)
  • Conclusions: HDE induces both rapid and sustained EGFR phosphorylation, and ERK1/2 is in turn activated downstream of EGFR activation. (cdc.gov)
  • Constitutive activation of ALK receptor tyrosine kinase may increase the proliferation of immature nerve cells, leading to neuroblastoma. (medlineplus.gov)
  • Conserved region 3 (CR3) is a catalytic protein kinase domain. (news-medical.net)
  • 1998). The Src SH2 domain has been shown to bind a phosphorylated tyrosine at the C-terminus of the same molecule resulting inactivation of enzyme activity by rearrangement of catalytic center in the kinase domain (reviewed in Hubbard et al. (lu.se)
  • The protein product of the gene is a phosphatase that negatively controls the phosphoinositide 3-kinase-signaling pathway for regulating cell growth and survival by dephosphorylating the 3 position of phosphoinositide. (medscape.com)
  • Serving a critical role in cell signaling, the class I family of phosphoinositide 3-kinases (PI3Ks) catalyze the phosphorylation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] to generate PI(3,4,5) P 3 . (elifesciences.org)
  • Phosphatidylinositol 3-kinases (PI3Ks) are important signaling molecules that phosphorylate the 3′ OH position of the inositol ring of phosphoinositides (PIs), generating the second messengers PI(3)P, PI(3,4)P 2 , and PI(3,4,5)P 3 ( 4 , 17 ). (asm.org)
  • Use of effector domain mutants of Rac suggest that Nischarin acts downstream of Rac, probably at the level of PAK-family kinases. (nih.gov)
  • The majority of inositol lipids reside in membranes and serve as substrates for kinases, phosphatases, and phospholipases. (asm.org)
  • However, it is unclear how the activity of plexin-B1 and its downstream effectors is regulated by its ligand Sema4D. (rupress.org)
  • We focus on six 'core' effectors that operate in almost all these species - members of the Pak, WASP/WAVE, formin, lipid-kinase, IQGAP and NADPH oxidase families. (biomedcentral.com)
  • Our studies concentrate on identification of downstream effector molecules triggered by the NPM/ALK kinase. (upenn.edu)
  • These second messengers recruit the downstream effector molecules. (asm.org)
  • Moreover, we generated a signature of 8 genes co-expressed with ACVRL1 across different tumor types and characterized the c-type lectin domain containing protein (CLEC)14A as a potential downstream target of ACVRL1. (lu.se)
  • ARNT-dependent HIF-2 transcriptional activity is not sufficient to regulate downstream target genes in neuroblastoma. (lu.se)
  • The master kinase LKB1 is a key regulator of several cellular processes, including cell proliferation, cell polarity and cellular metabolism. (sdbonline.org)
  • Although the specific function of ALK receptor tyrosine kinase is unknown, it is thought to act early in development to help regulate the proliferation of nerve cells. (medlineplus.gov)
  • Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). (ebi.ac.uk)
  • Thus integrins modulate the efficiency of the Erk (extracellular-signal-regulated kinase)/MAP kinase (mitogen-activated protein kinase) pathway, acting at several distinct levels. (nih.gov)
  • The NPM/ALK kinase is constitutively activated and highly oncogenic. (upenn.edu)
  • As a result, the kinase and the downstream signaling pathway are constantly turned on (constitutively activated). (medlineplus.gov)
  • Expression of ALK in malignant T cells is typically due to the t(2;5) translocation resulting in formation of the fusion gene which encodes a 80-kDa hybrid protein that contains portion of the nuclear protein nucleophosmin (NPM) joined to the entire cytoplasmic portion of the receptor tyrosine kinase ALK. (upenn.edu)
  • Mutations in the ALK gene change single protein building blocks (amino acids) in ALK receptor tyrosine kinase. (medlineplus.gov)
  • This phenomenon, known as gene amplification, results in overexpression of ALK receptor tyrosine kinase. (medlineplus.gov)
  • After dimerization, the kinase is tagged with a marker called a phosphate group (a cluster of oxygen and phosphorus atoms) in a process called phosphorylation. (medlineplus.gov)
  • ILK is composed of three domains, an N-terminal ankryin domain, a pleckstrin homology domain, and a putative kinase domain. (jneurosci.org)
  • A concomitant mutation was detected in 51% of Mouse monoclonal to HER-2 23% of and 33% of kinase-impaired mutations but only mutations in neuroendocrine carcinomas. (ecologicalsgardens.com)
  • Atomic resolution permitted the study of interface mutations capable of disrupting the MST4-MO25 interaction or the kinase-domain-mediated homodimerization. (rcsb.org)
  • VEGFA-165 signals by activating its receptor tyrosine kinase VEGF receptor-2 (VEGFR-2). (jneurosci.org)
  • Because another growth/trophic factor that signals via a receptor tyrosine kinase (brain derived neurotrophic factor) elicits a long-lasting facilitation of respiratory motor activity in the phrenic nerve, we tested the hypothesis that VEGFA-165 elicits similar phrenic motor facilitation (pMF). (jneurosci.org)
  • Little is known about how the kinase activity-deficient RYKs transduce Wnt signals. (biologists.com)
  • Although low-affinity ligands induced phosphorylation of the Cd3 chains of the T cell receptor and the interaction of Cd3 with the Zap70 kinase as strongly as high-affinity ligands, they failed to activate Zap70 to the same extent. (nature.com)
  • In conclusion, glucose ingestion prior to a sprint exercise profoundly affects Thr172- AMPKα phosphorylation and its downstream signaling during the recovery period. (ulpgc.es)
  • This study reports that LKB1 binds to Phosphoinositide-dependent kinase (PDK1) by a conserved binding motif. (sdbonline.org)
  • Integrin-linked kinase (ILK) is a major structural adaptor protein governing signaling complex formation and cytoskeletal dynamics. (jneurosci.org)
  • Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. (cardiff.ac.uk)
  • We have shown that both cAMP-dependent protein kinase and PAKs (p21-activated kinases) play a role in integrin regulation of the Erk pathway, acting primarily at the level of Raf-1. (nih.gov)
  • According to the kinetic proofreading model, antigen discrimination properties could be explained by the gradual amplification of small differences in binding affinities as the signal is transduced downstream of the T cell receptor. (nature.com)
  • 3. Mechanisms of malignant cell transformation by the chimeric NPM/ALK kinase. (upenn.edu)
  • Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK) defines a distinct type of T-cell lymphoma. (upenn.edu)
  • The process begins when the kinase is stimulated at the cell surface and then attaches to a similar kinase (dimerizes). (medlineplus.gov)
  • The activated kinase is able to transfer a phosphate group to another protein inside the cell, which is activated as a result. (medlineplus.gov)
  • Mutated or overexpressed ALK receptor tyrosine kinase no longer requires stimulation from outside the cell to be phosphorylated. (medlineplus.gov)
  • Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients. (ebi.ac.uk)
  • See More Use our definitive endoderm (DE) differentiation kit to obtain functional DE cells that are capable of downstream differentiation to hepatic, intestinal, pancreatic and pulmonary cells. (stemcell.com)