Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For identification of the protein-tyrosine kinases that are expressed in embryo stomach and gastric cancer, a 16-day rat embryo stomach and two human gastric cancer cDNA expression libraries were screened with an anti-phosphotyrosine antibody. Eight cDNAs encoding protein-tyrosine kinase were isolated, and Northern blot analysis revealed that five out of eight clones were highly expressed in rat embryo stomach, but not in adult rat stomach. From nucleotide sequence analysis, these five cDNAs were identified as elk, erk, esk, TTK and fyn, respectively. We report here that the expression levels of two families of receptor type tyrosine kinase genes, elk/erk and esk/TTK are developmentally regulated in rat stomach and highly expressed in human gastric cancer tissues. These findings suggest that elk/erk and esk/TTK genes play important roles in embryonic development and carcinogenesis of the stomach.
 ...
PMID:Identification of protein-tyrosine kinase genes preferentially expressed in embryo stomach and gastric cancer. 768 22

We report here the sequence of RPK1 (for Regulatory cell Proliferation Kinase), a new Saccharomyces cerevisiae gene coding for a protein with sequence similarities to serine/threonine protein kinases. The protein sequence of 764 amino acids includes an amino-terminal domain (residues 1-410), which may be involved in regulation of the kinase domain (residues 411-764). The catalytic domain of Rpk1 is not closely related to other known yeast protein kinases but exhibits strong homology to a newly discovered group of mammalian kinases (PYT, TTK, esk) with serine/threonine/tyrosine kinase activity. Null alleles of RPK1 are lethal and thus this gene belongs to the small group of yeast protein kinase genes that are essential for cell growth. In addition, eliminating the expression of RPK1 gives rise to the accumulation of non-viable cells with less than a 1 N DNA content suggesting that cells proceed into mitosis without completion of DNA synthesis. Therefore, the Rpk1 kinase may function in a checkpoint control which couples DNA replication to mitosis. The level of the RPK1 transcript is extremely low and constant throughout the mitotic cycle. However it is regulated during cellular differentiation, being decreased in alpha-factor-treated a cells and increased late in meiosis in a/alpha diploids. Taken together, our results suggest that Rpk1 is involved in a pathway that coordinates cell proliferation and differentiation.
 ...
PMID:RPK1, an essential yeast protein kinase involved in the regulation of the onset of mitosis, shows homology to mammalian dual-specificity kinases. 802 80

We have recently isolated the cDNA for a unique human 97-kDa kinase, TTK, by expression screening of a cDNA expression library using anti-phosphotyrosine antibodies. When expressed in Escherichia coli, TTK can phosphorylate serine, threonine, and tyrosine residues. Thus TTK appears to belong to a newly described family of kinases able to phosphorylate all three hydroxy amino acids. This family of multispecific kinases includes several other kinases involved in cell cycle progression. In support of a possible role in regulating cell cycle progression, TTK message is readily detected in rapidly proliferating tissues in vivo including testes, thymus, bone marrow, and many malignant tumors, but not in benign tissues with a low proliferative rate in vivo. To determine the effect of cell activation and cell cycle progression on TTK expression, we measured TTK mRNA and protein levels as well as kinase activity in freshly isolated T cells or IL-2-expanded T cell blasts activated to proliferate by the addition of a variety of mitogens. TTK mRNA levels, protein levels, and kinase activity were greatly enhanced when either freshly isolated PBL or T cell blasts were activated by cross-linking the TCR complex by mitogenic lectins or by bypassing the TCR with phorbol esters and cation ionophores. Incubation with IL-2 increased TTK expression in PBL blasts, which proliferate in response to IL-2, but not in fresh PBL, which do not proliferate in response to IL-2. TTK expression was blocked by either cyclosporin A or FK520, which inhibit IL-2 production and could be recovered by the addition of exogenous IL-2. Furthermore, TTK expression was prevented by incubation of the cells with rapamycin, which blocks IL-2 signaling. Thus, TTK expression in T cells appears to be a consequence of IL2-induced cell proliferation. Agonist-induced TTK expression was a delayed event occurring 12 to 24 h after activation of PBL blasts and 48 to 72 h after activation of fresh PBL. TTK protein and mRNA expression increased in both fresh PBL and T cell blasts concurrently with passage of cells through S phase as indicated by [3H]TdR incorporation and cell cycle analysis of propidium iodide-stained cells. TTK mRNA and protein levels reached a maximum as cells entered the G2 phase of the cell cycle. These results were confirmed by cell cycle blockade studies with aphidicolin and nocodazole wherein TTK protein levels are not detected in cells in G1 and are readily detectable in cells in the S and G2 phases of the cell cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:IL-2-induced expression of TTK, a serine, threonine, tyrosine kinase, correlates with cell cycle progression. 825 11

TTK is a novel protein kinase detectable in all proliferating human cells and tissues. Expression of the TTK gene is markedly reduced or absent in resting cells and in tissues with a low proliferative index. In view of the apparent association between TTK gene expression and cell proliferation, we examined the regulation of this protein kinase during transit of the cell cycle. We found very low levels of TTK mRNA and protein in starved cells. When cells are induced to enter the cell cycle, levels of TTK mRNA, protein and kinase activity increase at the G1/S phase of the cell cycle and peak in G2/M. TTK mRNA levels, as well as kinase activity, drop sharply in early G1, whereas protein levels are largely maintained. TTK may play a role in cell cycle control.
 ...
PMID:Cell cycle dependent regulation of the protein kinase TTK. 830 7

The expression of the Drosophila segmentation gene fushi tarazu (ftz) is controlled at the level of transcription. The proximal enhancer, located approximately 3.4 kb upstream of the transcription start site, directs lacZ fusion gene expression in a ftz-like seven-stripe pattern in transgenic fly embryos. We have taken a biochemical approach to identify DNA-binding proteins that regulate ftz gene expression through the proximal enhancer. DNase I footprinting and methylation interference experiments with staged Drosophila embryo nuclear extracts identified nine protein binding sites in the proximal enhancer. Ten different sequence-specific DNA-binding complexes that interact with eight of these sites were identified. Some interact with multiple sites, while others bind to single sites in the enhancer. Two of the complexes that interact with multiple sites appear to contain the previously described ftz regulators, FTZ-F1 and TTK/FTZ-F2. These in vitro studies allowed us to narrow down the proximal enhancer to a 323-bp DNA fragment that contains all of the protein binding sites. Expression directed by this minimal enhancer element in seven ftz-like stripes in transgenic embryos is identical to that directed by the full-length enhancer. Internal deletions of several sites abolish reporter gene expression in vivo. Thus, the ftz proximal enhancer, like other cell-type-specific eukaryotic enhancers, interacts with an array of proteins that are expected to mediate the establishment, maintenance, and repression of transcription of the ftz gene in seven stripes in the developing embryo.
 ...
PMID:Multiple proteins interact with the fushi tarazu proximal enhancer. 835

We have screened a collection of transposable-element-induced mutations for those which dominantly modify the extra R7 phenotype of a hypomorphic yan mutation. The members of one of the identified complementation groups correspond to disruptions of the tramtrack (ttk) gene. As heterozygotes, ttk alleles increase the percentage of R7 cells in yan mutant eyes. Just as yan mutations increase ectopic R7 cell formation, homozygous ttk mutant eye clones also contain supernumerary R7 cells. However, in contrast to yan, the formation of these cells in ttk mutant eye tissue is not necessarily dependent on the activity of the sina gene. Furthermore, although yan mutations dominantly interact with mutations in the Ras1, Draf, Dsor1, and rolled (rl) genes to influence R7 cell development, ttk mutations only interact with yan and rl gene mutations to affect this signaling pathway. Our data suggest that yan and ttk both function to repress inappropriate R7 cell development but that their mechanisms of action differ. In particular, TTK activity appears to be autonomously required to regulate a sina-independent mechanism of R7 determination.
 ...
PMID:Loss of tramtrack gene activity results in ectopic R7 cell formation, even in a sina mutant background. 864 23

A retrospective study of the surgical management of 41 cerebellopontine angle (CPA) meningiomas was performed. All patients were treated by a single surgeon (TTK) over a 25 year period (1967-1992). There were 13 males, 28 females with a median age of 53.5 years. The median follow-up after surgery was 9 years (range 2-20.4 years). Tumours were classified anatomically into six groups (lateral, midpetrosal, petroclival, internal auditory meatal, Meckel's cave and inferior). Only the petroclival tumours posed difficulties with complete resection (achieved in 7 out of 16) and for most of them a transtentorial transpetrous approach was used. In other groups, complete resection was achieved in all patients. There were four recurrences (two mid-petrosal, one petroclival, one internal auditory meatal), three of which had complete macroscopic resection at the initial operation.
 ...
PMID:Meningiomas of the cerebellopontine angle. A report of 41 cases. 867 60

Tat protein mediates transactivation of human immunodeficiency virus type 1 (HIV-1), which results in more-efficient transcript elongation. Since phosphorylation of C-terminal domain (CTD) of RNA polymerase II correlates with its enhanced processivity, we studied the properties of a Tat-associated CTD kinase derived from mitogenically stimulated human primary T lymphocytes (TTK). TTK binds to full-length Tat and specifically phosphorylates CTD and CDK2. This dual kinase activity is characteristic of CDK-activating kinase (CAK). The CTD kinase activity is induced upon mitogenic stimulation of primary T lymphocytes. Fractionation of T-cell lysate demonstrates that Tat-associated CTD kinase activity elutes in two peaks. About 60% of Tat-associated CTD kinase copurifies with CDK2 kinase activity and contains the CAK components CDK7 and cyclin H. The rest of Tat-associated kinase is free of CDK2 kinase activity and the CAK components and thus may represent a novel CTD kinase. The kinase activities of TTK are blocked by the adenosine analog 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB) as well as by the kinase inhibitor H8 at concentrations known to block transcript elongation. Importantly, the Tat-associated kinase markedly induced CAK. We suggest that the mechanism of Tat-mediated processive transcription of the HIV-1 promoter includes a Tat-associated CAK activator.
 ...
PMID:A human primary T-lymphocyte-derived human immunodeficiency virus type 1 Tat-associated kinase phosphorylates the C-terminal domain of RNA polymerase II and induces CAK activity. 931 22

Aneuploidy is a characteristic of the majority of human cancers, and recent work has suggested that mitotic checkpoint defects play a role in its development. To further explore this issue, we isolated a novel human gene, MAD2B (MAD2L2), which is homologous to the spindle checkpoint gene MAD2 (MAD2L1). We determined the chromosomal localization of it and other spindle checkpoint genes, including MAD1L1, MAD2, BUB3, TTK (MPS1L1), and CDC20. In addition, we resolved the genomic intron-exon structure of the human BUB1 gene. We then searched for mutations in these genes in a panel of 19 aneuploid colorectal tumors. No new mutations were identified, suggesting that genes yet to be discovered are responsible for most of the checkpoint defects observed in aneuploid cancers.
 ...
PMID:Characterization of MAD2B and other mitotic spindle checkpoint genes. 1036 50

Activation of the HIV-1 promoter by the virally encoded Tat protein is characterized by efficient processive transcription, mediated by host cell factors that are tethered to the promoter with the Tat-TAR RNA complex. Importantly, viral gene activation has been shown to be stimulated in mitogenically induced cells, although the link between cell cycle regulation and viral gene activation is unclear. We reported a Tat-associated CAK/CTD kinase from mitogenically induced primary human T-cells (TTK) (S. Nekhai et al., 1997, J. Virol. 71, 7436-7441). Here, biological activity of the kinase has been studied by direct microinjection at the individual-cell level. The TTK-dependent Tat response is maximal during G1 phase as shown by co-injection with Tat protein in cells synchronized at the various stages of the cell cycle. The cell cycle dependence of the Tat response was confirmed by inhibiting G0 --> G1 progression with the expression of dominant negative mutant Ras(Asn17) or the cyclin-dependent kinase CDK4. The results support a mechanism whereby transactivation of the HIV promoter is regulated by cell growth signal transduction pathways that target the Tat cofactor.
 ...
PMID:Cell cycle-dependent stimulation of the HIV-1 promoter by Tat-associated CAK activator. 1063 11


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