Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is now a growing body of evidence which suggests links between the regulation of protein synthesis and the disruption of cell behaviour that typifies cancer. This directed issue of the International Journal of Biochemistry and Cell Biology presents several review articles of relevance to this field. The topics covered include the significance of the regulation and overexpression of polypeptide chain initiation factors for cell transformation and malignancy, the role of mRNA structure in the control of synthesis of key growth regulatory proteins, the actions of the eIF2 alpha-specific protein kinase PKR in the control cell growth and apoptosis, and the involvement of the elongation factor eEF1 in oncogenesis. The purpose of this article is to give an overview of the field and to indicate where we may expect developments to occur in the next few years.
...
PMID:Translational control: the cancer connection. 1021 39

Epidemiological and experimental data suggest that dietary fiber and fat are major determinants of colorectal cancer. However, the mechanisms by which these dietary constituents alter the incidence of colon cancer have not been elucidated. Evidence indicates that dominant gain-of-function mutations short-circuit protooncogenes and contribute to the pathogenesis of cancer. Therefore, we began to dissect the mechanisms whereby dietary fat and fiber, fed during the initiation, promotion and progression stages of colon tumorigenesis, regulate ras p21 localization, expression and mutation frequency. Male Sprague-Dawley rats (140) were provided with corn oil or fish oil and pectin or cellulose plus or minus the carcinogen azoxymethane (AOM) in a 2 x 2 x 2 factorial design and killed after 34 weeks. We have previously shown adenocarcinoma incidence in these animals to be 70.3% (52/74) for corn oil + AOM and 56.1% (37/66) for fish oil + AOM (P < 0.05). Total ras expression as well as ras membrane:cytosol ratio was 4- to 6-fold higher in colon tumors than in mucosa from AOM- or saline-injected rats. Expression of ras in the mucosal membrane fraction was 13% higher for animals fed corn oil compared with fish oil feeding (P < 0.05), which is noteworthy since ras must be localized at the plasma membrane to function. The elevated ras membrane:cytosol ratio in tumors was not due to increased farnesyl protein transferase activity or prenylation state, as nearly all detectable ras was in the prenylated form. Phosphorylated p42 and p44 mitogen activated protein kinase (ERK) expression was two-fold higher in tumor extracts compared with uninvolved mucosa from AOM- and saline-injected rats (P < 0.05). The frequency of K-ras mutations was not significantly different between the various groups, but there was a trend toward a greater incidence of mutations in tumors from corn oil fed rats (85%) compared with fish oil fed rats (58%). Our results indicate that the carcinogen-induced changes in ras expression and membrane localization are associated with the in vivo activation of the ERK pathway. In addition, suppression of tumor development by dietary n-3 polyunsaturated fatty acids may be partly due to a combined effect on colonic ras expression, membrane localization, and mutation frequency.
...
PMID:Carcinogen and dietary lipid regulate ras expression and localization in rat colon without affecting farnesylation kinetics. 1033 94

Regulation of beta-catenin stability is essential for Wnt signal transduction during development and tumorigenesis. It is well known that serine-phosphorylation of beta-catenin by the Axin-glycogen synthase kinase (GSK)-3beta complex targets beta-catenin for ubiquitination-degradation, and mutations at critical phosphoserine residues stabilize beta-catenin and cause human cancers. How beta-catenin phosphorylation results in its degradation is undefined. Here we show that phosphorylated beta-catenin is specifically recognized by beta-Trcp, an F-box/WD40-repeat protein that also associates with Skp1, an essential component of the ubiquitination apparatus. beta-catenin harboring mutations at the critical phosphoserine residues escapes recognition by beta-Trcp, thus providing a molecular explanation for why these mutations cause beta-catenin accumulation that leads to cancer. Inhibition of endogenous beta-Trcp function by a dominant negative mutant stabilizes beta-catenin, activates Wnt/beta-catenin signaling, and induces axis formation in Xenopus embryos. Therefore, beta-Trcp plays a central role in recruiting phosphorylated beta-catenin for degradation and in dorsoventral patterning of the Xenopus embryo.
...
PMID:beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. 1033 77

Integrin-linked kinase (ILK) is a recently identified cytoplasmic protein serine/threonine kinase implicated in integrin-, growth factor- and Wnt-signaling pathways. It contains several structurally conserved motifs including ankyrin repeats, pleckstrin-homology (PH) domain and protein kinase catalytic domain that are critical for signal transduction. Recent studies have documented that ILK plays important roles in bi-directional ( and ) transmembrane signaling pathways via integrins and other proteins, leading to regulation of cell adhesion, growth, survival, extracellular matrix deposition and potentially differentiation. Furthermore, ILK is implicated in tumorigenesis and ILK appears to be a useful diagnostic marker of certain human tumors. The identification of novel ILK-associated proteins will provide a better understanding of how ILK functions in intracellular signal transduction cascades and tumorigenesis.
...
PMID:Integrin-linked kinase and associated proteins (review). 1034 Dec 84

The conserved Ipl1 protein kinase is essential for proper chromosome segregation and thus cell viability in the budding yeast Saccharomyces cerevisiae. Its human homologue has been implicated in the tumorigenesis of diverse forms of cancer. We show here that sister chromatids that have separated from each other are not properly segregated to opposite poles of ipl1-2 cells. Failures in chromosome segregation are often associated with abnormal distribution of the spindle pole-associated Nuf2-GFP protein, thus suggesting a link between potential spindle pole defects and chromosome missegregation in ipl1 mutant cells. A small fraction of ipl1-2 cells also appears to be defective in nuclear migration or bipolar spindle formation. Ipl1 associates, probably directly, with the novel and essential Sli15 protein in vivo, and both proteins are localized to the mitotic spindle. Conditional sli15 mutant cells have cytological phenotypes very similar to those of ipl1 cells, and the ipl1-2 mutation exhibits synthetic lethal genetic interaction with sli15 mutations. sli15 mutant phenotype, like ipl1 mutant phenotype, is partially suppressed by perturbations that reduce protein phosphatase 1 function. These genetic and biochemical studies indicate that Sli15 associates with Ipl1 to promote its function in chromosome segregation.
...
PMID:Sli15 associates with the ipl1 protein kinase to promote proper chromosome segregation in Saccharomyces cerevisiae. 1038 19

The cyclin-dependent kinase (cdk) inhibitors are key regulators of cell cycle progression. p27 and p21 are members of the Cip/Kip family of cdk inhibitors and regulate cell growth by inactivating cell cycle stage-specific CDK-cyclin complexes. Because down-regulation of osteoprogenitor proliferation is a critical step for osteoblast differentiation, we investigated expression of p27 and p21 during development of the osteoblast phenotype in rat calvarial osteoblasts and in proliferating and growth-inhibited osteosarcoma ROS 17/2.8 cells. Expression of these proteins indicates that p21, which predominates in the growth period, is related to proliferation control. p27 levels are maximal postproliferatively, suggesting a role in the transition from cell proliferation to osteoblast differentiation. We directly examined the role of p27 during differentiation of osteoprogenitor cells derived from the bone marrow (BM) of p27-/- mice. BM cells from p27 null mice exhibited increased proliferative activity compared with BM cells from wild-type mice and formed an increased number and larger size of osteoblastic colonies, which further differentiated to the mineralization stage. Although p27-/- adherent marrow cells proliferate faster, they retain competency for differentiation, which may result, in part, from observed higher p21 levels compared with wild type. Histological studies of p27-/- bones also showed an increased cellularity in the marrow cavity compared with the p27+/+. The increased proliferation in bone does not lead to tumorigenesis, in contrast to observed adenomas in the null mice. Taken together, these findings indicate that p27 plays a key role in regulating osteoblast differentiation by controlling proliferation-related events in bone cells.
...
PMID:The cell cycle regulator p27kip1 contributes to growth and differentiation of osteoblasts. 1044 85

ATW8 was a unique opportunity to review the complex and growing field of ataxia-telangiectasia (A-T) research and to cross-fertilize ideas for new experimental designs. A-T biology now encompasses human and mouse neurology, neurobiology, immunology, radiobiology, cell signalling, cell cycle checkpoints, gametogenesis, and oncogenesis, as well as radiotherapy, cancer epidemiology, premature aging, cytogenetics, and DNA repair mechanisms. By an as yet undetermined mechanism, the ATM protein appears to sense double strand breaks (DSB) during meiosis or mitosis, or breaks consequent to the damage of free radicals which are generated during the metabolism of food. As a protein kinase, ATM then directly phosphorylates p53 and interacts with many other molecules involved in homologous and nonhomologous DSB repair, as well as in cell signalling. Some of these molecule targets include: c-abl, ATR, chk-1, chk-2, RPA, BRCA1, BRCA2, NFkappaB/IkappaB alpha, beta-adaptin, and perhaps ATM itself. Thus, ATM is a "hierarchical kinase," initiating many pathways simultaneously. Parallel sessions or longer meetings will clearly be necessary for future A-T workshops.
...
PMID:Eighth International Workshop on Ataxia-Telangiectasia (ATW8). 1044 4

The identification of genes that confer a growth advantage on neoplastic cells and the understanding of the genetic mechanism(s) responsible for their activation have made possible a direct genetic approach to cancer treatment using nucleic acid therapeutics. Moreover, the ability to block the expression of individual genes that promote carcinogenesis provides a powerful tool to explore the molecular basis of normal growth regulation, as well as the opportunity for therapeutic intervention. One technique for turning off a single activated gene is the use of antisense oligodeoxynucleotides and their analogs for inhibition of gene expression. The serine/threonine kinases are involved in mediating intracellular responses to external signals, such as growth factors, hormones, and neurotransmitters, and are involved in cell proliferation and oncogenesis. Described herein are recent studies supporting the potential use of oligonucleotides targeting these kinases as chemotherapeutic agents for cancer treatment. The serine/threonine kinases included here are protein kinase A, protein kinase C, and c-raf-1 kinase.
...
PMID:Antisense oligonucleotide inhibition of serine/threonine kinases: an innovative approach to cancer treatment. 1045 18

The Wnt signalling cascade is essential for the development of both invertebrates and vertebrates, and is altered during tumorigenesis. Although a general framework for Wnt signalling has been elucidated, not all of the components have been identified. Here we describe a serine kinase, casein kinase I (CKI), which was isolated by expression cloning in Xenopus embryos. CKI reproduces several properties of Wnt signals, including generation of complete dorsal axes, stabilization of beta-catenin and induction of genes that are direct targets of Wnt signals. Dominant-negative forms of CKI and a pharmacological blocker of CKI inhibited Wnt signals in Xenopus. Inhibiting CKI in Caenorhabditis elegans generated worms with a mom phenotype, indicative of a loss of Wnt signals. In addition, CKI bound to and increased the phosphorylation of dishevelled, a known component of the Wnt pathway. These data indicate that CKI may be a conserved component of the Wnt pathway.
...
PMID:Casein kinase I transduces Wnt signals. 1051 32

Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorigenic, and mutations that stabilize beta-catenin are found in various human cancers including colorectal cancer. To determine the role of stabilized beta-catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell-mediated homologous recombination, a mutant beta-catenin allele whose exon 3 was sandwiched by loxP sequences. When the germline heterozygotes were crossed with mice expressing Cre recombinase in the intestines, the serines and threonine encoded by exon 3 and to be phosphorylated by glycogen synthase kinase 3beta (GSK3beta) were deleted in the offspring intestines, which caused adenomatous intestinal polyps resembling those in Apc(Delta716) knockout mice. Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors.
...
PMID:Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. 1054 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---