Search results for "kinases"
showing 10 items of 929 documents
Transcriptional profiling reveals functional links between RasGrf1 and Pttg1 in pancreatic beta cells
2014
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License .
A novel serine/threonine kinase gene, STK33 , on human chromosome 11p15.3
2001
Human chromosomal region 11p15 is known to be associated with several diseases including predispositions to develop various tumor types. In search of candidate genes, a novel human kinase gene is described, STK33, which codes for a serine/threonine protein kinase. The gene was discovered by comparative genome analysis of human chromosome 11p15.3 and its orthologous region on distal mouse chromosome 7. Human STK33 gene contains 12 exons as has been determined by the comparison to the full-length transcript amplified from human uterus RNA. Transcripts are found in a variety of tissues in at least two alternatively spliced forms as revealed by reverse transcriptase-polymerase chain reaction, c…
Rapid cloning of cDNA ends polymerase chain reaction of G-protein-coupled receptor kinase 6: an improved method to determine 5′- and 3′-cDNA ends
1999
Abstract Rapid cloning of 5′- and 3′-cDNA ends polymerase chain reaction (5′-/3′-RACE-PCR) is useful to determine unknown 5′- and 3′-cDNA termini. Even if the method can yield complete cDNA sequences within a couple of days, the RACE procedure bears some characteristic traps and often results in amplification of unspecific PCR-products. Here we used improved 5′- and 3′-RACE-PCR protocols to obtain the complete cDNA sequence of the G-protein-coupled receptor kinase 6 (GRK6) from a rat brain cDNA library. The use of an anchored oligo-(dT) 16 -V-primer in the cDNA synthesis, the addition of single-sided PCR steps prior to the RACE-PCRs and the optimization of the dA-tailing reaction conditions…
Negative regulation of diacylglycerol kinase θ mediates adenosine-dependent hepatocyte preconditioning
2010
In liver ischemic preconditioning (IP), stimulation of adenosine A2a receptors (A2aR) prevents ischemia/reperfusion injury by promoting diacylglycerol-mediated activation of protein kinase C (PKC). By concerting diacylglycerol to phosphatidic acid, diacylglycerol kinases (DGKs) act as terminator of diacylglycerol signalling. This study investigates the role of DGK in the development of hepatocyte IP. DGK activity and cell viability were evaluated in isolated rat hepatocytes preconditioned by 10 min hypoxia followed by 10 min re-oxygenation or by the treatment with the A2aR agonist, CGS21680, and subsequently exposed to prolonged hypoxia. We observed that after IP or A2aR activation, a decre…
Molecular markers for germ cell differentiation in the demosponge Suberites domuncula
2004
Sponges (phylum Porifera) are simple metazoans for which no molecular information on gametogenesis and larval development is available. To support the current study, it was confirmed by histology that oocytes and larvae were produced by the demosponge Suberites domuncula. Three genes/expressed products from S. domuncula whose expression correlated with sexual reproduction were identified and characterized (they are used here as marker genes): i) a receptor tyrosine kinase (RTK) with sequence similarity in the tyrosine kinase domain to fibroblast growth factor receptors; ii) the sex-determining protein FEM1 and iii) the sperm associated antigen (SAA) of triploblasts. Antibodies against the e…
Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis
2012
Abstract Background Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality. Aims In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease. Methods A four-week daily dose of silibinin (20 mg/kg i.p.) was administrated to db/db mice fed a methionine–choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated. Results Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrit…
Hepatocellular expression of a dominant-negative mutant TGF-β type II receptor accelerates chemically induced hepatocarcinogenesis
2001
The potent growth-inhibitory activity of cytokines of the transforming growth factor-beta (TGF-beta) superfamily and their widespread expression in epithelia suggest that they may play an important role in the maintenance of epithelial homeostasis. To analyse TGF-beta mediated tumor suppressor activity in the liver, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in hepatocytes under control of the regulatory elements of the human C-reactive protein gene promoter. Transgenic animals exhibited constitutive and liver-specific transgene expression. The functional inactivation of the TGF-beta signaling pathway in transgenic hepatocytes was shown by redu…
PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia
2015
Malformations of cortical development containing dysplastic neuronal and glial elements, including hemimegalencephaly and focal cortical dysplasia, are common causes of intractable paediatric epilepsy. In this study we performed multiplex targeted sequencing of 10 genes in the PI3K/AKT pathway on brain tissue from 33 children who underwent surgical resection of dysplastic cortex for the treatment of intractable epilepsy. Sequencing results were correlated with clinical, imaging, pathological and immunohistological phenotypes. We identified mosaic activating mutations in PIK3CA and AKT3 in this cohort, including cancer-associated hotspot PIK3CA mutations in dysplastic megalencephaly, hemimeg…
Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice.
2018
It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TK…
Molecular mechanisms of carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of metformin
2019
AbstractCarfilzomib (Cfz), an irreversible proteasome inhibitor licensed for relapsed/refractory myeloma, is associated with cardiotoxicity in humans. We sought to establish the optimal protocol of Cfz-induced cardiac dysfunction, to investigate the underlying molecular-signaling and, based on the findings, to evaluate the cardioprotective potency of metformin (Met). Mice were randomized into protocols 1 and 2 (control and Cfz for 1 and 2 consecutive days, respectively); protocols 3 and 4 (control and alternate doses of Cfz for 6 and 14 days, respectively); protocols 5A and 5B (control and Cfz, intermittent doses on days 0, 1 [5A] and 0, 1, 7, and 8 [5B] for 13 days); protocols 6A and 6B (p…