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)

The interferon (IFN)-inducible double-stranded (ds) RNA-activated protein kinase (p68 kinase) is a physiologically important enzyme that regulates the rate of cellular and viral protein synthesis by phosphorylating and thereby inactivating the peptide chain initiation factor 2. We have generated a partial cDNA clone, which probably represents the murine p68 kinase, by reverse transcription-polymerase chain reaction (RT-PCR) using sequence information of the human p68 kinase. The 725-bp cDNA clone encoded the carboxyl-terminal 238 amino acid residues of the mouse kinase. It has 67% overall identity with the corresponding region of the human kinase. All the protein kinase catalytic domains are conserved in the mouse protein. Moreover, there are additional stretches of residues that are totally conserved between the two proteins. The functional equivalence of the two proteins was tested by constructing a chimeric cDNA that encoded a protein whose amino-terminal 364 residues were of human origin and carboxyl-terminal 187 residues were of mouse origin. The chimeric protein was as efficient as the human p68 kinase in binding to the dsRNA, autophosphorylating and phosphorylating exogenous substrate.
...
PMID:Construction and expression of an enzymatically active human-mouse chimeric double-stranded RNA-dependent protein kinase. 135 89

The kit protooncogene encodes a transmembrane tyrosine kinase related to the receptors for the platelet derived growth factor (PDGF-R) and the macrophage growth factor (CSF1-R), and was very recently shown to bind a stem cell factor. To compare signal transduction by the kit kinase with signaling by homologous receptors we constructed a chimeric protein composed of the extracellular domain of the epidermal growth factor receptor (EGF-R) and the transmembrane and cytoplasmic domains of kit. We have previously shown that the chimeric receptor transmits potent mitogenic and transforming signals in response to the heterologous ligand. Here we demonstrate that upon ligand binding, the ligand-receptor complex undergoes endocytosis and degradation and induces short- and long-term cellular effects. Examination of the signal transduction pathway revealed that the activated kit kinase strongly associates with phosphatidylinositol 3'-kinase activity and a phosphoprotein of 85 kd. In addition, the ligand-stimulated kit kinase is coupled to modifications of phospholipase C gamma and the Raf1 protein kinase. However, it does not lead to a significant change in the production of inositol phosphate. Comparison of our results with the known signaling pathways of PDGF-R and CSF1-R suggests that each receptor is coupled to a specific combination of signal transducers.
...
PMID:A specific combination of substrates is involved in signal transduction by the kit-encoded receptor. 170 85

A chimeric G alpha subunit cDNA, referred to as G alpha s/i(38), was constructed containing the complete 5'-untranslated region of G alpha s, the first 356 codons of the rat G alpha s and the last 36 codons and 428 base pairs of the 3'-untranslated region of the rat G alpha i cDNA. Transient expression of the G alpha s/i(38) protein in COS cells allowed detection of a chimeric protein which was recognized by antibodies generated against an internal G alpha s sequence as well as antibodies recognizing the carboxyl terminus of G alpha i2. Chinese hamster ovary cell clones stably expressing the chimeric G-protein alpha subunit transcript (G alpha s/i(38] demonstrated 1.5-2.5-fold constitutively elevated cyclic AMP levels and a 3-4-fold increase in the activity ratio of cyclic AMP-dependent protein kinase, although expression of the chimeric polypeptide could not be demonstrated presumably because of low expression of the mutant alpha s. Expression of the rat G alpha s transcript yielded clones that were similar to wild-type Chinese hamster ovary cells in regard to cyclic AMP levels and protein kinase activity. In the presence of methyl isobutylxanthine, a cyclic AMP phosphodiesterase inhibitor, cyclic AMP levels in clones expressing the G alpha s/i(38) transcript were 10-15-fold higher than G alpha s expressing clones. Adenylyl cyclase activation by guanosine 5'-O-(thiotriphosphate) (GTP gamma S) in membranes from clones expressing the G alpha s/i(38) transcript demonstrated a diminished lag time for maximal activation, indicating an increased relative GDP dissociation rate for the chimeric G alpha subunit and an increase in total adenylyl cyclase activity relative to wild-type G alpha s expressing clones. Cholate extracts from membranes of G alpha s/i(38) expressing clones, when mixed with cyc- S49 membranes, reconstituted an increased GTP gamma S-stimulated adenylyl cyclase activity and a diminished lag time for maximal activation compared to cholate extracts prepared from G alpha s-expressing clones. The G alpha s/i(38) construct confers a dominant constitutive activation of adenylyl cyclase when expressed in cells in the presence of a background of wild-type G alpha s.
...
PMID:Expression of a G alpha s/G alpha i chimera that constitutively activates cyclic AMP synthesis. 246 29

Philadelphia chromosome positive acute lymphocytic leukemia and chronic myelogenous leukemia are strongly associated with two distinct forms of bcr-abl chimeric protein, known as P190 and P210, respectively. By studying cDNA clones obtained from the cell line KBM-5, we identified two new bcr-abl transcripts. These are formed by alternative splicing of at least two exons to the known bcr exon 2. One novel transcript can encode a protein kinase of approximately 190 kd, while the other can direct the synthesis of a larger protein whose amino terminus remains to be defined. The alternative exons can be spliced also to the two normal bcr transcripts, reflecting the activation of a cryptic promoter. These messages were present at low abundance in two cases of blastic crisis but were not detected in the chronic phase. It is conceivable that the proteins encoded by the new bcr-abl mRNAs are involved in the transformation to the acute phase in some cases of chronic myelogenous leukemia.
...
PMID:Alternative 5' end of the bcr-abl transcript in chronic myelogenous leukemia. 291 4

The ret oncogene frequently has been found activated in papillary thyroid carcinomas. A previous characterization of ret activation revealed recombination of its tyrosine kinase domain and sequences derived from an uncharacterized locus (D10S170). The mechanism leading to this recombination was identified as a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with the breakpoints occurring where ret and D10S170 were mapped. To further characterize the activation of ret in papillary thyroid carcinomas, we have now isolated and sequenced a second type of ret oncogenic rearrangement not involving the D10S170 locus. The nucleotide sequence indicated that the transforming activity was created by the fusion of the ret tyrosine kinase domain with part of the RI alpha regulatory subunit of protein kinase A (PKA). This is the first example of an oncogenic activity involving a PKA gene. PKA is the main intracellular cyclic AMP receptor, and its RI alpha subunit gene is located on chromosome 17q. RI alpha-ret transcripts encode two isoforms of the chimeric protein (p76 and p81), which display constitutive tyrosine phosphorylation as well as a tyrosine kinase enzymatic activity. Under nonreducing conditions, both isoforms are found in a dimeric configuration because of both homo- and heterodimer formation. Thus, the in vivo activation of ret in human papillary thyroid carcinomas is provided by the fusion of its tyrosine kinase domain with different genes and can be mediated by different mechanisms of gene rearrangement.
...
PMID:Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A. 767 53

The MPS1 gene has been previously identified by a mutant allele that shows defects in spindle pole body (SPB) duplication and cell cycle control. The SPB is the centrosome-equivalent organelle in the yeast Saccharomyces cerevisiae, and it nucleates all the microtubules in the cell. We report the isolation of the MPS1 gene, which encodes an essential protein kinase homolog. The MPS1 open reading frame has been fused to those that encode the LexA protein or the GST protein and both of these constructs function in yeast. The fusion proteins have been affinity-purified from yeast extracts and the GST chimeric protein has been found to be a phosphoprotein. Both proteins have been used to demonstrate intrinsic in vitro protein kinase activity of Mps1p against exogenous substrates and itself (autophosphorylation). A mutation predicted to abolish kinase function not only eliminates in vitro protein kinase activity, but also behaves like a null mutation in vivo, suggesting that kinase activity contributes to the essential function of the protein. Phosphoamino acid analysis of substrates phosphorylated by Mps1p indicates that this kinase can phosphorylate serine, threonine and tyrosine residues, identifying Mps1p as a dual specificity protein kinase.
...
PMID:Yeast spindle pole body duplication gene MPS1 encodes an essential dual specificity protein kinase. 773 18

Lipopolysaccharide (LPS), a highly conserved component of the outer membrane of gram-negative bacteria, stimulates macrophages to release various cytokine and eicosanoid mediators of the immune response. The mechanism by which LPS stimulates these cells is poorly characterized. One of the most rapid LPS-stimulated events is the phosphorylation and activation of the p42 and p44 isoforms of mitogen-activated protein (MAP) kinase. We wished to examine the role of MAP kinase in LPS-induced signaling in murine macrophages by activating MAP kinase independently of LPS. An expression vector encoding a Raf-1:estrogen receptor (ER) chimeric protein was transfected into the murine macrophage cell line RAW 264.7. Activation of this chimeric protein (delta Raf-1:ER) by estradiol resulted in rapid and prolonged activation of MAP kinase, as expected from previous results implicating Raf-1 as an upstream activator of this signaling cascade. LPS stimulation induced accumulation of MAP kinase phosphatase 1 messenger RNA, whereas delta Raf-1:ER activation did not, perhaps accounting for the more prolonged activation of MAP kinase seen in response to delta Raf-1:ER activation. Similarly, activation of DNA binding by the transcription factor, nuclear factor (NF) kappa B, as assessed by electrophoretic mobility shift assay, occurred in response to LPS stimulation but not in response to delta Raf-1:ER activation or phorbol myristate acetate (PMA) stimulation. Using an enzyme-linked immunosorbent assay for murine tumor necrosis factor alpha (TNF-alpha), we found that LPS and PMA stimulation and delta Raf-1:ER activation induced secretion of TNF-alpha, although the amount of TNF-alpha secreted in response to delta Raf-1:ER activation and PMA stimulation was approximately 20-fold less than that secreted in response to LPS. Correspondingly, accumulation of TNF-alpha messenger RNA was weakly induced by delta Raf-1:ER activation or PMA stimulation, whereas strong induction was noted in response to LPS. These results suggest that Raf-1 or PMA activation of MAP kinase in murine macrophages is sufficient for a small amount of TNF-alpha production and secretion in the absence of NF-kappa B activation, but LPS stimulation involves additional signaling events, such as NF-kappa B activation, that augment the response seen with activation of MAP kinase alone.
...
PMID:Activation of Raf-1 and mitogen-activated protein kinase in murine macrophages partially mimics lipopolysaccharide-induced signaling events. 779 Aug 14

The cloning of the negative growth regulatory gene, p21Sdi1, has led to the convergence of the fields of cellular senescence, cell cycle regulation and tumor suppression. This gene was first cloned as an inhibitor of DNA synthesis that was overexpressed in terminally non-dividing senescent human fibroblasts (SD11) and later as a p53 transactivated gene (WAF1) and a Cdk-interacting protein (CIP1, p21) that inhibited cyclin-dependent kinase activity. To identify the active region(s) of p21Sdi1, cDNA constructs encoding various deleted forms of the protein were analyzed. Amino acids 22-71 were found to be the minimal region required for DNA synthesis inhibition. Amino acids 49-71 were involved in binding to Cdk2, and constructs deleted in this region expressed proteins that were unable to inhibit Cdk2 kinase activity in vitro. The latter stretch of amino acids shared sequence similarity with amino acids 60-76 of the p27Kip1 protein, another Cdk inhibitor. Point mutations made in p21Sdi1 in this region confirmed that amino acids common to both proteins were involved in DNA synthesis inhibition. Additionally, a chimeric protein, in which amino acids 49-65 of p21Sdi1 were substituted with amino acids 60-76 of p27Kip1, had almost the same DNA synthesis inhibitory activity as the wild-type protein. The results indicate that the region of sequence similarity between p21Sdi1 and p27Kip1 encodes an inhibitory motif characteristic of this family of Cdk inhibitors.
...
PMID:Identification of the active region of the DNA synthesis inhibitory gene p21Sdi1/CIP1/WAF1. 785 44

An earlier report has shown that eight viral proteins with a common amino acid sequence (R/P)RA(P/S)R are nucleotidylyated in vitro by nuclear extracts from cells infected with herpes simplex virus 1. One, the product of the alpha 22 gene, is nucleotidylylated in the absence of viral proteins made late in infection. A chimeric protein (GST22P) consisting of amino acids 50-200 of the alpha 22 coding sequence fused to the C terminus of the glutathione S-transferase was nucleotidylylated by enzymes in nuclear extracts of infected or mock-infected cells and also by a casein kinase II enzyme purified from the sea star. The enzyme did not nucleotidylylate common casein kinase II substrates (casein, phosvitin) and the reaction was inhibited by heparin. The results are consistent with the hypothesis that nucleotidylylation of the eight viral proteins involves casein kinase II.
...
PMID:Casein kinase II specifically nucleotidylylates in vitro the amino acid sequence of the protein encoded by the alpha 22 gene of herpes simplex virus 1. 799 47

We report that the small tumor (small-t) antigen of simian virus 40 (SV40) forms complexes with nuclear protein phosphatase 2A (PP2A) and regulates the phosphorylation and transcriptional transactivation function of the cyclic AMP (cAMP)-regulatory element binding protein (CREB). PP2A coimmunoprecipitated with small t from nuclear extracts from HepG2 cells expressing small t or from rat liver nuclear extracts to which recombinant small t was added. Protein phosphatase 1 was not detected in small-t immunoprecipitates. In HepG2 cells expressing small t, dibutyryl-cAMP (Bt2cAMP) stimulated the phosphorylation of CREB 65-fold, whereas CREB phosphorylation was stimulated only 5- to 8-fold by Bt2cAMP in cells not expressing small t. Small t also inhibited the dephosphorylation of cAMP-dependent protein kinase (PKA)-phosphorylated CREB in rat liver nuclear extracts. In cells expressing small t, Bt2cAMP-stimulated transcription from the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter was enhanced over the level of transcription from the PEPCK promoter in cells not expressing small t. Small t also enhanced Bt2cAMP-stimulated transcription from a Gal4-responsive promoter in cells expressing a chimeric protein containing the Gal4 DNA-binding domain linked to the CREB transactivation domain. However, small t did not stimulate transcription either from a 5' deletion mutant of the PEPCK promoter that is not able to bind CREB or from the Gal4-responsive promoter in the absence of the Gal4-CREB protein. These data suggest that small t enhances Bt2cAMP-stimulated gene transcription by inhibiting the dephosphorylation of PKA-phosphorylated CREB by nuclear PP2A. These findings support previous observations that nuclear PP2A is the primary phosphatase that dephosphorylates PKA-phosphorylated CREB.
...
PMID:Simian virus 40 small tumor antigen inhibits dephosphorylation of protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. 806 21


1 2 3 4 Next >>

---