Sentences with phrase «kinase activity in»

Serum thymidine kinase activity in canine splenic hemangiosarcoma.

Leucine reduces the duration of insulin - induced PI 3 - kinase activity in rat skeletal muscle.

Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate - 1 (IRS - 1)- associated phosphatidylinositol 3 - kinase activity in muscle.

He received his MSc and his PhD in Molecular Pharmacology and Oncology at the Institute for Higher Studies of the University of Ferrara exploring the role of LRRK2 kinase activity in mouse model of model of familial Parkinson's disease and performing studies focused on the phenomena underlying neurodegeneration.

To cite a few instances, polymerase chain reaction (PCR), a molecular method developed over three decades ago, has been widely applied in disease diagnosis, disease mechanism deciphering, and prognosis prediction; the elucidation of tyrosine kinase activity in cancer cells has led to the development of novel drugs for cancer treatment; and the identification of proteins and genetic molecules by molecular methods as biomarkers for disease diagnosis and prognosis has been drawing great interest.

Axitinib, a drug used to treat renal cell carcinoma, has been shown to be effective at inhibiting the Abl kinase activity in patients with BCR - ABL1 (T315I).

Not exact matches

An approach often used in treating CML is to block the Bcr - Abl activity using tyrosine kinase inhibitors (TKIs).

In the melanoma cell to its right, red indicates activity of a signaling molecule called PI3 - kinase.

Using the nanodiscs, the team elucidated the activation mechanism of receptor kinase AgrC and discovered a key regulatory hotspot in the kinase that could greatly affect its activity.

Our results suggest that frequent overexpression of Aurora Kinase in cancer may reduce RUNX3 transcription activity, leading to cell division and formation of tumours.

Transmission of signals in a cell is controlled by the coordinated activity of two families of enzymes: protein tyrosine kinases, which add a phosphate group to proteins, and protein tyrosine phosphatases, which remove them.

Images taken with a fluorescent microscope show the activity of a kinase (green) in tumor cells (bottom) compared to normal cells (top).

Some of its members have similar structures, which has led some researchers to propose that the activity of these kinases is probably regulated in a similar manner and, therefore, may be targeted with similar medications.

The kinase activity of RIPK1 mediates hypothermia and lethality in a mouse model of TNF - induced shock, reflecting the hyperinflammatory state of systemic inflammatory response syndrome (SIRS), where the proinflammatory «cytokine storm» has long been viewed as detrimental.

We used the janus kinase (JAK) inhibitor baricitinib with IFN - blocking activity in vitro, to ameliorate disease.

They were then able to use a compound recently discovered by Harvard University investigator Professor Nathanael Gray to block the activity of one of the kinases important in HCV replication, MAP4K2.

They found that an enzyme called DNA - dependent protein kinase, or DNA - PK, increases in activity with age.

The activity of tyrosine kinases is typically regulated in an auto - inhibitory fashion, but the BCR - Abl fusion gene codes for a protein that is «always on» or continuously activated leading to unregulated cell division (i.e. cancer).

A role for casein kinase II phosphorylation in the regulation of IRF - 1 transcriptional activity.

Disruption of Ca2 + - dependent cell - matrix adhesion enhances c - Src kinase activity, but causes dissociation of the c - Src / FAK complex and dephosphorylation of tyrosine - 577 of FAK in carcinoma cells.

Casein Kinase 1δ Activity: A Key Element in the Zebrafish Circadian Timing System.

In addition to being integral to cell biology, tyrosine kinases also present targets for new anticancer therapies: One of the most highly touted, rationally designed anticancer compounds, Gleevec, inhibits an oncogenic tyrosine kinase whose aberrant activity fuels the rampant growth of cells in patients with chronic myeloid leukemiIn addition to being integral to cell biology, tyrosine kinases also present targets for new anticancer therapies: One of the most highly touted, rationally designed anticancer compounds, Gleevec, inhibits an oncogenic tyrosine kinase whose aberrant activity fuels the rampant growth of cells in patients with chronic myeloid leukemiin patients with chronic myeloid leukemia.

It has been observed that mutated BRAF not only upregulates its own kinase activity, but also that of MEK and ERK, which in turn promotes cell proliferation [34].

Since November 2013, as part of SGC, Clara mainly investigates different subfamilies of kinases involved in alternative splicing through phosphorylation - mediated regulation of SR proteins activity.

PACAP regulates immediate catecholamine release from adrenal chromaffin cells in an activity - dependent manner through a protein kinase C - dependent pathway.

Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryo.

The Ser / Thr kinase activity of the Yersinia protein kinase A (YpkA) is necessary for full virulence in the mouse, mollifying phagocytes, and disrupting the eukaryotic cytoskeleton.

Quizartinib inhibits FLT3 kinase activity and induced about a 50 % composite response rate among patients with FLT3 - ITD mutations in phase I and II studies, said lead author Mahesh Swaminathan, MD of the University of Texas MD Anderson Cancer Center in Houston.

Fructose selectively modulates c - jun N - Terminal kinase activity and insulin signaling in rat primary hepatocytes..

The mutation is acquired, is present in a variable proportion of granulocytes, alters a highly conserved valine present in the negative regulatory JH2 domain, and is predicted to dysregulate kinase activity.

Larotrectinib, a highly selective inhibitor of all three tropomyosin receptor kinase (TRK) proteins, was recently shown to have marked and sustained antitumor activity in patients with TRK fusion — positive cancers, according to an analysis of three phase I and II cohorts.

Through interaction with the cdk / cyclin complexes, p21waf1 / cip1 modulates their kinase activity, resulting in cell growth arrest (10).

The basal and B - RAF - stimulated kinase activities of a third variant are unaltered but its activation by RAS is significantly reduced, suggesting that it may act in a dominant - negative manner to modulate pathway signaling.

Pim - 3, a Proto - Oncogene with Serine / Threonine Kinase Activity, Is Aberrantly Expressed in Human Pancreatic Cancer and Phosphorylates Bad to Block Bad - Mediated Apoptosis in Human Pancreatic Cancer Cell Lines

Regardless, our data support a role for ABL kinases in the regulation of TAZ protein abundance and activity in breast cancer cells.

These results demonstrate that ABL kinase activity is required for osteolytic metastasis in breast cancer and suggest that pharmacological inhibition of the ABL kinases may be an effective treatment for bone metastasis.

Studies by ours and other groups have shown that a number of EphA2 and EphA3 mutations inactivate Eph receptor canonical signaling by disrupting ephrin binding or kinase activity, consistent with a role of canonical signaling in tumor suppression.

Flavopiridol inhibits several cellular kinases and has demonstrated cytostatic and cytotoxic activity in vitro and in vivo in numerous human tumor cell lines and xenograft models (including human breast, prostate, and lung carcinoma) at clinically achievable concentrations.

It has been shown in imatinib - resistant CML that drug resistance conferred by mutations does not necessarily correlate with proliferative advantage and increased kinase activity.34 Other, non-activating mutations or drug - resistance mechanisms, might be acquired by tumor cells.

Low levels of glutathione peroxidase 1 activity in selenium - deficient mouse liver affect c - Jun N - terminal kinase activation and p53 phosphorylation on Ser - 15 in pro-oxidant-induced aponecrosis.

In 2005, the identification of an activating mutation in JAK2 (the V617F mutation) as a STAT5 - activating and disease - causing genetic alteration in a significant proportion of patients with myeloproliferative neoplasms (MPNs) has emphasized the oncogenic role of the JAK tyrosine kinases in hematologic malignancies.2 — 5 JAK2 is a member of the Janus tyrosine kinase family comprising three other mammalian non-receptor tyrosine kinases (JAK1, JAK3 and TYK2) that associate with cytokine receptors lacking intrinsic kinase activity to mediate cytokine - induced signal transduction and activation of STAT transcription factors.6 All JAKs share a similar protein structure and contain a tyrosine kinase domain at the C - terminus flanked by a catalytically inactive pseudokinase domain with kinase - regulatory activity, by an atypical SH2 domain and by a FERM domain that mediates association to the membrane - proximal region of the cytokine receptors.7, 8 Soon after the discovery of JAK2 V617F, we and others described that activating JAK1 mutations are relatively common in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.In 2005, the identification of an activating mutation in JAK2 (the V617F mutation) as a STAT5 - activating and disease - causing genetic alteration in a significant proportion of patients with myeloproliferative neoplasms (MPNs) has emphasized the oncogenic role of the JAK tyrosine kinases in hematologic malignancies.2 — 5 JAK2 is a member of the Janus tyrosine kinase family comprising three other mammalian non-receptor tyrosine kinases (JAK1, JAK3 and TYK2) that associate with cytokine receptors lacking intrinsic kinase activity to mediate cytokine - induced signal transduction and activation of STAT transcription factors.6 All JAKs share a similar protein structure and contain a tyrosine kinase domain at the C - terminus flanked by a catalytically inactive pseudokinase domain with kinase - regulatory activity, by an atypical SH2 domain and by a FERM domain that mediates association to the membrane - proximal region of the cytokine receptors.7, 8 Soon after the discovery of JAK2 V617F, we and others described that activating JAK1 mutations are relatively common in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.in JAK2 (the V617F mutation) as a STAT5 - activating and disease - causing genetic alteration in a significant proportion of patients with myeloproliferative neoplasms (MPNs) has emphasized the oncogenic role of the JAK tyrosine kinases in hematologic malignancies.2 — 5 JAK2 is a member of the Janus tyrosine kinase family comprising three other mammalian non-receptor tyrosine kinases (JAK1, JAK3 and TYK2) that associate with cytokine receptors lacking intrinsic kinase activity to mediate cytokine - induced signal transduction and activation of STAT transcription factors.6 All JAKs share a similar protein structure and contain a tyrosine kinase domain at the C - terminus flanked by a catalytically inactive pseudokinase domain with kinase - regulatory activity, by an atypical SH2 domain and by a FERM domain that mediates association to the membrane - proximal region of the cytokine receptors.7, 8 Soon after the discovery of JAK2 V617F, we and others described that activating JAK1 mutations are relatively common in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.in a significant proportion of patients with myeloproliferative neoplasms (MPNs) has emphasized the oncogenic role of the JAK tyrosine kinases in hematologic malignancies.2 — 5 JAK2 is a member of the Janus tyrosine kinase family comprising three other mammalian non-receptor tyrosine kinases (JAK1, JAK3 and TYK2) that associate with cytokine receptors lacking intrinsic kinase activity to mediate cytokine - induced signal transduction and activation of STAT transcription factors.6 All JAKs share a similar protein structure and contain a tyrosine kinase domain at the C - terminus flanked by a catalytically inactive pseudokinase domain with kinase - regulatory activity, by an atypical SH2 domain and by a FERM domain that mediates association to the membrane - proximal region of the cytokine receptors.7, 8 Soon after the discovery of JAK2 V617F, we and others described that activating JAK1 mutations are relatively common in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.in hematologic malignancies.2 — 5 JAK2 is a member of the Janus tyrosine kinase family comprising three other mammalian non-receptor tyrosine kinases (JAK1, JAK3 and TYK2) that associate with cytokine receptors lacking intrinsic kinase activity to mediate cytokine - induced signal transduction and activation of STAT transcription factors.6 All JAKs share a similar protein structure and contain a tyrosine kinase domain at the C - terminus flanked by a catalytically inactive pseudokinase domain with kinase - regulatory activity, by an atypical SH2 domain and by a FERM domain that mediates association to the membrane - proximal region of the cytokine receptors.7, 8 Soon after the discovery of JAK2 V617F, we and others described that activating JAK1 mutations are relatively common in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.in ALL development allowing for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.in AML and breast cancer patients.10

Structure of the BRAF: MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling

In addition, caffeine may increase the activity of several signaling enzymes, including the calcium - dependent protein kinase and protein kinase B (also called Akt), which have roles in muscle glucose uptake during and after exercisIn addition, caffeine may increase the activity of several signaling enzymes, including the calcium - dependent protein kinase and protein kinase B (also called Akt), which have roles in muscle glucose uptake during and after exercisin muscle glucose uptake during and after exercise.

Altogether, beside the mutations targeting the JH1 / JH2 interface, the other activating mutations found in this study point to two other hotspots for the regulation of JAK enzymatic activity: the hinge region and in the loop formed between β2 - and β3 - strand in the kinase domain.

We found that canonical signaling by the EphB4 receptor is low in breast cancer cells and that ephrin - induced stimulation of EphB4 kinase activity inhibits breast cancer cell malignancy in culture and tumor growth in vivo (Figure 1A) through inhibition of the CRK proto - oncogene.

A Harpin Binding Site in Tobacco Plasma Membranes Mediates Activation of the Pathogenesis - Related Gene HIN1 Independent of Extracellular Calcium but Dependent on Mitogen - Activated Protein Kinase Activity

In addition, at least some Eph receptors can also signal through non-canonical mechanisms that are independent of ligand binding and kinase activity, for example through interplay with other receptor tyrosine kinase families and with serine / threonine kinases.

These activities are independent of ephrin binding and / or kinase activity and their mechanism is not well understood but in some cases depends on Eph receptor phosphorylation on serine / threonine residues (red circle).

Susan Amara, USA - «Regulation of transporter function and trafficking by amphetamines, Structure - function relationships in excitatory amino acid transporters (EAATs), Modulation of dopamine transporters (DAT) by GPCRs, Genetics and functional analyses of human trace amine receptors» Tom I. Bonner, USA (Past Core Member)- Genomics, G protein coupled receptors Michel Bouvier, Canada - Molecular Pharmacology of G protein - Coupled Receptors; Molecular mechanisms controlling the selectivity and efficacy of GPCR signalling Thomas Burris, USA - Nuclear Receptor Pharmacology and Drug Discovery William A. Catterall, USA (Past Core Member)- The Molecular Basis of Electrical Excitability Steven Charlton, UK - Molecular Pharmacology and Drug Discovery Moses Chao, USA - Mechanisms of Neurotophin Receptor Signaling Mark Coles, UK - Cellular differentiation, human embryonic stem cells, stromal cells, haematopoietic stem cells, organogenesis, lymphoid microenvironments, develomental immunology Steven L. Colletti, USA Graham L Collingridge, UK Philippe Delerive, France - Metabolic Research (diabetes, obesity, non-alcoholic fatty liver, cardio - vascular diseases, nuclear hormone receptor, GPCRs, kinases) Sir Colin T. Dollery, UK (Founder and Past Core Member) Richard M. Eglen, UK Stephen M. Foord, UK David Gloriam, Denmark - GPCRs, databases, computational drug design, orphan recetpors Gillian Gray, UK Debbie Hay, New Zealand - G protein - coupled receptors, peptide receptors, CGRP, Amylin, Adrenomedullin, Migraine, Diabetes / obesity Allyn C. Howlett, USA Franz Hofmann, Germany - Voltage dependent calcium channels and the positive inotropic effect of beta adrenergic stimulation; cardiovascular function of cGMP protein kinase Yu Huang, Hong Kong - Endothelial and Metabolic Dysfunction, and Novel Biomarkers in Diabetes, Hypertension, Dyslipidemia and Estrogen Deficiency, Endothelium - derived Contracting Factors in the Regulation of Vascular Tone, Adipose Tissue Regulation of Vascular Function in Obesity, Diabetes and Hypertension, Pharmacological Characterization of New Anti-diabetic and Anti-hypertensive Drugs, Hypotensive and antioxidant Actions of Biologically Active Components of Traditional Chinese Herbs and Natural Plants including Polypehnols and Ginsenosides Adriaan P. IJzerman, The Netherlands - G protein - coupled receptors; allosteric modulation; binding kinetics Michael F Jarvis, USA - Purines and Purinergic Receptors and Voltage-gated ion channel (sodium and calcium) pharmacology Pain mechanisms Research Reproducibility Bong - Kiun Kaang, Korea - G protein - coupled receptors; Glutamate receptors; Neuropsychiatric disorders Eamonn Kelly, Prof, UK - Molecular Pharmacology of G protein - coupled receptors, in particular opioid receptors, regulation of GPCRs by kinasis and arrestins Terry Kenakin, USA - Drug receptor pharmacodynamics, receptor theory Janos Kiss, Hungary - Neurodegenerative disorders, Alzheimer's disease Stefan Knapp, Germany - Rational design of highly selective inhibitors (so call chemical probes) targeting protein kinases as well as protein interaction inhibitors of the bromodomain family Andrew Knight, UK Chris Langmead, Australia - Drug discovery, GPCRs, neuroscience and analytical pharmacology Vincent Laudet, France (Past Core Member)- Evolution of the Nuclear Receptor / Ligand couple Margaret R. MacLean, UK - Serotonin, endothelin, estrogen, microRNAs and pulmonary hyperten Neil Marrion, UK - Calcium - activated potassium channels, neuronal excitability Fiona Marshall, UK - GPCR molecular pharmacology, structure and drug discovery Alistair Mathie, UK - Ion channel structure, function and regulation, pain and the nervous system Ian McGrath, UK - Adrenoceptors; autonomic transmission; vascular pharmacology Graeme Milligan, UK - Structure, function and regulation of G protein - coupled receptors Richard Neubig, USA (Past Core Member)- G protein signaling; academic drug discovery Stefan Offermanns, Germany - G protein - coupled receptors, vascular / metabolic signaling Richard Olsen, USA - Structure and function of GABA - A receptors; mode of action of GABAergic drugs including general anesthetics and ethanol Jean - Philippe Pin, France (Past Core Member)- GPCR - mGLuR - GABAB - structure function relationship - pharmacology - biophysics Helgi Schiöth, Sweden David Searls, USA - Bioinformatics Graeme Semple, USA - GPCR Medicinal Chemistry Patrick M. Sexton, Australia - G protein - coupled receptors Roland Staal, USA - Microglia and neuroinflammation in neuropathic pain and neurological disorders Bart Staels, France - Nuclear receptor signaling in metabolic and cardiovascular diseases Katerina Tiligada, Greece - Immunopharmacology, histamine, histamine receptors, hypersensitivity, drug allergy, inflammation Georg Terstappen, Germany - Drug discovery for neurodegenerative diseases with a focus on AD Mary Vore, USA - Activity and regulation of expression and function of the ATP - binding cassette (ABC) transporters

For example, our past work showed that two conserved tyrosine phosphorylation sites in the juxtamembrane segment of the Eph receptors not only mediate association with binding partners but also regulate receptor kinase activity.