In addition, our data evidence that LA via the Rho -
associated kinase - mediated pathway promotes stress fiber formation, which exerts a main role in the morphological changes associated with apoptotic cell death.
Overall stem cell colony formation efficiency following single cell isolation and flow cytometry was still quite low (∼ 0.5 %) despite the use of the Rho -
associated kinase inhibitor but consistent results were obtained.
Interleukin - 1 receptor -
associated kinase - 1 plays an essential role for Toll - like receptor (TLR) 7 - and TLR9 - mediated interferon - α induction.
MicroRNA - 93 inhibits inflammatory responses and cell apoptosis after cerebral ischemia reperfusion by targeting interleukin - 1 receptor -
associated kinase 4.
Not exact matches
By analysing skin biopsies post-injection, the researchers found that the excessive inflammation was
associated with activation of the p38 MAP
kinase pathway.
The research team, including Soumen Paul, Ph.D.,
associate professor, Arindam Paul, Ph.D., assistant professor, and Ossama Tawfik, professor, M.D., Ph. D., all in the Department of Pathology and Laboratory Medicine, and their colleagues, studied atypical protein
kinase c lambda / iota signaling during the invasive progression of triple - negative breast cancer.
Among patients with advanced non-small cell lung cancer without a mutation of a certain gene (EGFR), conventional chemotherapy, compared with treatment using epidermal growth factor receptor tyrosine
kinase inhibitors, was
associated with improvement in survival without progression of the cancer, but not with overall survival, according to a study in the April 9 issue of JAMA.
Maternal alcohol consumption prior to and during pregnancy significantly affects cognitive functions in offspring, which may be related to changes in cyclin - dependent
kinase 5 because it is
associated with modulation of synaptic plasticity and impaired learning and memory.
«Through our collaboration with DiscoverX, we screened a large set of compounds that we call Published
Kinase Inhibitor Set 2, and these results allowed us to reach the halfway point in constructing the KCGS» said David Drewry, a research
associate professor at the UNC Eshelman School of Pharmacy and SGC - UNC principal investigator who is leading the project to develop the
Kinase Chemogenomic Set.
«We know dysregulation of a protein enzyme called multifunctional CaM
kinase II plays a role in disrupting sodium channel function in cardiac disease, but it was a matter of determining how this occurred and whether we could we prevent it for therapeutic benefit,» said Hund, an
associate professor of biomedical engineering at The Ohio State University.
In a proof - of - concept study, Fourches and Ash looked at the ERK2
kinase — an enzyme
associated with several types of cancer — and a group of 87 known ERK2 inhibitors, ranging from very active to inactive.
This factor is required for Tat trans - activation and is a substrate of an
associated cellular
kinase.
Moreover, our previous study found that regular use of aspirin after diagnosis was
associated with longer survival among the 15 % to 30 % of patients with colorectal cancer and with a mutation in phosphatidylinositol -4,5-bisphosphate 3 -
kinase, catalytic subunit alpha (PIK3CA [NCBI Entrez Gene 5290]-RRB-, one of the PI3K family genes.30 Markedly improved survival
associated with aspirin according to PIK3CA status was also found in an analysis within a separate clinical trial cohort.31 Further investigations for the joint effect of these genes would be helpful to better understand the underlying molecular mechanisms of aspirin, NSAIDs, and colorectal cancer.
Chan AC, Iwashima M, Trck CW, Weiss A. ZAP - 70: a 70kd protein - tyrosine
kinase that
associates with the TCRzeta chain.
NF - κB - activating
kinase -
associated protein 1 participates in TLR3 / Toll — IL - 1 homology domain - containing adapter molecule -1-mediated IFN regulatory factor 3 activation.
The Abl gene expresses a membrane -
associated protein, a tyrosine
kinase, and the BCR - Abl transcript is also translated into a tyrosine
kinase.
Toll / IL -1 receptor domain - containing adaptor inducing IFN - β (TRIF)
associates with TNF receptor -
associated factor 6 and TANK - binding
kinase 1, and activates two distinct transcription factors, NF - κB and IFN - regulatory factor - 3, in the Toll - like receptor signaling.
Adeno -
associated virus replication induces a DNA damage response coordinated by DNA - dependent protein
kinase.
So we looked to see whether middle T also had an
associated protein
kinase activity, and we were delighted to find that it did.»
Activation of Src
kinase Lyn by the Kaposi sarcoma —
associated herpesvirus K1 protein: implications for lymphomagenesis.
P16 binds to cyclin - dependent
kinases 4 and 6 (CDK4 and CDK6) and inhibits phosphorylation of Rb, which remains
associated with the transcription factor, E2F.
It is known that one of the pathways involved in cutaneous cancer is mediated through CDKN2A which is a gene
associated with melanoma dysregulation through its pro-oncogenic products p16INK4a (Cyclin - Dependent
Kinase Inhibitor P16) and p14ARF (P14 alternate open reading frame)[28].
Expression of the receptor tyrosine
kinase Tie2 in neoplastic glial cells is
associated with integrin beta1 - dependent adhesion to the extracellular matrix.
«Two groups had reported a
kinase activity
associated with the viral Src protein,» recalls Hunter: Marc Collett and Ray Erikson, then at the University of Colorado Medical Center, and Mike Bishop and Harold Varmus, then at the University of California, San Francisco.
[48] Mutations in GNAQ or GNA11 occur in the majority of uveal melanomas and drive oncogenesis via activation of the phospholipase C / protein
kinase C (PKC), Rho / Rac, and Yes -
associated protein pathways.
The genome encodes a large number of novel receptor
kinases and contains expansions of a variety of gene families, including those
associated with virulence.
mTOR is a serine / threonine protein
kinase that forms two distinct protein complexes within cells: one with the regulatory -
associated protein of TOR (raptor) and another with the rapamycin - insensitive companion (rictor; refs.
«As a result, researchers have used the presence of IBs and heightened
kinase activity as a proxy for measuring LRRK2's harmful effects, rather than measuring LRRK2 levels directly,» explained Dr. Finkbeiner, who is the
associate director of neurological research at Gladstone as well as a professor at the University of California, San Francisco, with which Gladstone is affiliated.
To address this question we study various microtubule -
associated proteins (molecular motors and MAPs) and their regulators (
kinases, phosphatases and the small GTPase Ran during M - phase).
Along the same lines, in non-small cell lung cancer (NSCLC), acquired resistance to Gefitinib / Erlotinib
kinase inhibitors has also been
associated with a secondary mutation of the gatekeeper Thr790 residue of the epidermal growth factor receptor (EGFR).
The initial model for STAT signaling involves a specific cytokine binding to its cognate receptor and promoting the transphosphorylation of receptor
associated tyrosine
kinases from the Janus - activated
kinase family (JAK).
It belongs to the MAGUK family of proteins (membrane -
associated guanylate
kinase homologues), that also includes SAP90, PSD - 95 and many others (for review, see Montgomery et al 2004).
Inhibitory role of alpha6beta 4 -
associated erbB - 2 and phosphoinositide 3 -
kinase in keratinocyte haptotactic migration dependent on alpha3beta1 integrin.
These mutant
kinases are attractive therapeutic targets, as demonstrated by the efficacy of imatinib in BCR - ABL — positive chronic myelogenous leukemia (CML), 5 as well as in MPD
associated with activating alleles involving PDGFRA or PDGFRB.2, 6,7 In addition, activating mutations in the FLT3 receptor tyrosine
kinase are the most common genetic event in acute myeloid leukemia (AML), and specific inhibitors of the FMS - like tyrosine
kinase 3 (FLT3) have entered late - stage clinical trials.8 Although mutations in tyrosine
kinases and in other genes have been identified in a subset of MPD and AML, in many cases the genetic events that contribute to the molecular pathogenesis of these diseases remain unknown.
Abbreviations: ASC, apoptosis -
associated speck - like protein containing a caspase - recruitment domain; ATM, adipose - tissue - resident macrophage; BAT, brown adipose tissue; CCR2, CC chemokine receptor 2; CHOP, C / EBP (CCAAT / enhancer - binding protein)- homologous protein; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; ER, endoplasmic reticulum; GPCR, G - protein - coupled receptor; HIF, hypoxia - inducible factor; IFNγ, interferon γ; IKK, inhibitor of nuclear factor κB
kinase; IL, interleukin; IRS - 1, insulin receptor substrate - 1; JNK, c - Jun N - terminal
kinase; LDL, low - density lipoprotein; Ldlr, LDL receptor; LXR, liver X receptor; MCP - 1, monocyte chemoattractant protein 1; miRNA, microRNA; mTOR, mammalian target of rapamycin; NAFLD, non-alcoholic fatty liver disease; NF - κB, nuclear factor κB; NLRP3, NLR (nucleotide - binding - domain - and leucine - rich - repeat - containing) family, pyrin - domain - containing 3; oxLDL, oxidized LDL; PKR, double - stranded RNA - dependent protein
kinase; PPAR, peroxisome - proliferator - activated receptor; STAT6, signal transducer and activator of transcription 6; SVF, stromal vascular fraction; TLR, Toll - like receptor; TNFα, tumour necrosis factor α; UPR, unfolded protein response; WAT, white adipose tissue
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.10
Death -
associated protein
kinase (DAPK) and signal transduction: fine - tuning of autophagy in Caenorhabditis elegans homeostasis.
Interestingly, the most commonly mutated set of genes were those involved in epigenetic modification (25 % of tumors) followed by transcriptional regulators and MAP
kinase -
associated genes (12 - 15 %).
DAXX
associates with RelB, a transcription factor of the NF - κB family that directly controls the expression of numerous apoptosis - and autophagy - relevant genes, including tumor suppressor protein
kinases DAPK1 / 3 [1; 2].
Common and rare variants
associating with serum levels of creatine
kinase and lactate dehydrogenase.
Abbreviations: Aβ, amyloid β - peptide; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; Ambra1, activating molecule in Beclin -1-regulated autophagy; AMPK, AMP - activated protein
kinase; APP, amyloid precursor protein; AR, androgen receptor; Atg, autophagy - related; AV, autophagic vacuole; Bcl, B - cell lymphoma; BH3, Bcl - 2 homology 3; CaMKKβ, Ca2 + - dependent protein
kinase kinase β; CHMP2B, charged multivesicular body protein 2B; CMA, chaperone - mediated autophagy; 2 ′ 5 ′ ddA, 2 ′, 5 ′ - dideoxyadenosine; deptor, DEP - domain containing mTOR - interacting protein; DRPLA, dentatorubral pallidoluysian atrophy; 4E - BP1, translation initiation factor 4E - binding protein - 1; Epac, exchange protein directly activated by cAMP; ER, endoplasmic reticulum; ERK1 / 2, extracellular - signal - regulated
kinase 1/2; ESCRT, endosomal sorting complex required for transport; FAD, familial AD; FDA, U.S. Food and Drug Administration; FIP200, focal adhesion
kinase family - interacting protein of 200 kDa; FoxO3, forkhead box O3; FTD, frontotemporal dementia; FTD3, FTD linked to chromosome 3; GAP, GTPase - activating protein; GR, guanidine retinoid; GSK3, glycogen synthase
kinase 3; HD, Huntington's disease; hiPSC, human induced pluripotent stem cell; hVps, mammalian vacuolar protein sorting homologue; IKK, inhibitor of nuclear factor κB
kinase; IMPase, inositol monophosphatase; IP3R, Ins (1,4,5) P3 receptor; I1R, imidazoline - 1 receptor; JNK1, c - Jun N - terminal
kinase 1; LC3, light chain 3; LD, Lafora disease; L - NAME, NG - nitro - L - arginine methyl ester; LRRK2, leucine - rich repeat
kinase 2; MIPS, myo - inositol -1-phosphate synthase; mLST8, mammalian lethal with SEC13 protein 8; MND, motor neuron disease; mTOR, mammalian target of rapamycin; mTORC, mTOR complex; MVB, multivesicular body; NAC, N - acetylcysteine; NBR1, neighbour of BRCA1 gene 1; NOS, nitric oxide synthase; p70S6K, ribosomal protein S6
kinase - 1; PD, Parkinson's disease; PDK1, phosphoinositide - dependent
kinase 1; PE, phosphatidylethanolamine; PI3K, phosphoinositide 3 -
kinase; PI3KC1a, class Ia PI3K; PI3KC3, class III PI3K; PI3KK, PI3K - related protein
kinase; PINK1, PTEN - induced
kinase 1; PKA, protein
kinase A; PLC, phospholipase C; polyQ, polyglutamine; PS, presenilin; PTEN, phosphatase and tensin homologue deleted from chromosome 10; Rag, Ras - related GTP - binding protein; raptor, regulatory -
associated protein of mTOR; Rheb, Ras homologue enriched in brain; rictor, rapamycin - insensitive companion of mTOR; SBMA, spinobulbar muscular atrophy; SCA, spinocerebellar ataxia; SLC, solute carrier; SMER, small - molecule enhancer of rapamycin; SMIR, small - molecule inhibitor of rapamycin; SNARE, N - ethylmaleimide - sensitive factor - attachment protein receptor; SOD1, copper / zinc superoxide dismutase 1; TFEB, transcription factor EB; TOR, target of rapamycin; TSC, tuberous sclerosis complex; ULK1, UNC -51-like
kinase 1; UVRAG, UV irradiation resistance -
associated gene; VAMP, vesicle -
associated membrane protein; v - ATPase, vacuolar H + - ATPase; Vps, vacuolar protein sorting
We also have research interests in cellular regulation by ADP - ribosylation, which links epigenetics to metabolism; lipid
kinases; and sphingolipid biosynthesis, which has strong links to both inflammation and cancer, and where mutations in the various proteins involved are
associated with a variety of rare diseases.
First, Nanog opened two key cellular pathways, known as Rho -
associated protein
kinase (ROCK) and Transforming growth factor beta (TGF - β).
This
kinase receptor has important clinical relevance, as EGFR deregulated signalling is strongly
associated with cancer.
Abbreviations: AMPAR, AMPA receptor; AS, Angelman syndrome; BDNF, brain - derived neurotrophic factor; CaMKII, α - calcium / calmodulin - dependent protein
kinase II; CGN, cerebellar granule neuron; co-IP, coimmunoprecipitation; DG, dentate gyrus; ERK, extracellular signal - regulated
kinase; fEPSP, field excitatory postsynaptic potential; Gab1, Grb2 -
associated binder 1; HFS, high frequency stimulation; IGF, insulin - like growth factor; LTP, long - term potentiation; PSD - 95, postsynaptic density protein - 95; SYN, synaptophysin; WT, wild type
Expression of the MAP
kinase phosphatase DUSP4 is
associated with microsatellite instability in colorectal cancer (CRC) and causes increased cell proliferation.
Five Xanthomonas type III effectors suppress cell death induced by components of immunity -
associated MAP
kinase cascades
Myosin IIA's activity is regulated by RhoA and Rho -
associated protein
kinase (ROCK) signaling.
Free fatty acid - induced insulin resistance is
associated with activation of protein
kinase C theta and alterations in the insulin signaling cascade.
Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate - 1 (IRS - 1)-
associated phosphatidylinositol 3 -
kinase activity in muscle.