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

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

Raf-1 serine-threonine protein kinase has the hallmarks of a critical switch that connects growth factor receptor activation at the cell membrane with transcriptional events in the nucleus. We show by use of Raf-1 dominant-negative mutants that Raf-1 is required for serum-, TPA-, and Ras-induced expression from the oncogene-responsive element in the polyomavirus enhancer. The minimal region of Raf-1 that displays this dominant-negative phenotype (Raf-C4) contains a cysteine finger motif. Raf-C4 appears to function by titrating out a Raf-1-activating factor that is induced by Ras following serum or TPA treatment of NIH-3T3 cells. In addition, we show that Raf-1 and Ras cooperate in trans-activation through the oncogene-responsive element and that the cysteine-rich region is necessary for this effect.
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PMID:Serum-, TPA-, and Ras-induced expression from Ap-1/Ets-driven promoters requires Raf-1 kinase. 131 69

Herpes simplex virus type 2 (HSV-2) gene US3 encodes a serine-threonine protein kinase. We previously described the isolation of a US3-inactivated mutant which is able to replicate in Vero cells but not in murine macrophages. To learn more about the biological role of the US3 protein kinase, we have sought to identify the target proteins of the enzyme. Studies of in vitro phosphorylation with extracts of infected cells demonstrate that the US3 protein kinase is involved in phosphorylation of the UL12 alkaline nuclease in vitro, suggesting that the nuclease is a possible target of the protein kinase.
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PMID:The US3 protein kinase of herpes simplex virus type 2 is associated with phosphorylation of the UL12 alkaline nuclease in vitro. 748 95

The serine-threonine protein kinase Raf-1 is an important signal transducer in mitogenesis, phosphorylating and activating mitogen-activated protein (MAP) kinase kinase. Raf-1 activation in vivo is dependent on Ras, but the mechanism of Raf activation is unknown. The ability of preparations of plasma membranes to activate exogenous (His)6-Raf-1 was studied. Plasma membranes of v-Ras-transformed NIH 3T3 cells, but not parental cells, enhanced MAP kinase kinase kinase (MAPKKK) activity dependent on addition of (His)6-Raf-1 and ATP/Mg. Treatment of membranes with concentrations of Bacillus cereus phosphatidylcholine-specific phospholipase C that activated Raf-1 in vivo failed to enhance MAPKKK activity in vitro. Activation of (His)6-Raf-1 in vitro by membranes was dependent on binding to Ras. Membranes from v-Src-transformed cells also activated (His)6-Raf-1 and synergized with v-Ras membranes. Serum-treatment of NIH 3T3 cells stimulated the ability of membranes to activate (His)6-Raf-1. Activated (His)6-Raf-1 could be recovered on Ni(2+)-agarose, and this methodology was used to demonstrate that activation by membranes was ATP dependent. These findings demonstrate Ras- and ATP-dependent step(s) for Raf-1 activation by plasma membranes in vitro.
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PMID:Activation of (His)6-Raf-1 in vitro by partially purified plasma membranes from v-Ras-transformed and serum-stimulated fibroblasts. 793 2

Sequential protein kinase reactions involve the phosphorylation and activation of multiple kinases in a pathway. The growth factor receptor tyrosine kinase regulation of the mitogen-activated protein kinase (MAPK) pathway was defined in 1993. The MAPK pathway involves sequential protein kinase reactions. Notable advances were made in defining tyrosine kinase receptor regulation of Ras, and these discoveries were combined with the identification of Raf-1, a serine-threonine protein kinase in the MAPK pathway, as an effector for Ras GTP.
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PMID:Sequential protein kinase reactions controlling cell growth and differentiation. 802 15

Herpes simplex virus type 2 (HSV-2) gene US3 has been shown to encode a serine-threonine protein kinase. In this study, we have tried to identify target proteins of the US3 protein kinase using a US3 lacZ insertion mutant of HSV-2. When permeabilized cells were labelled with [gamma-32P]ATP under the optimum conditions for the US3 enzyme, the most striking difference between wild-type HSV-2 strain 186- and mutant-infected cells was observed in the phosphorylation of proteins ranging in M(r) values from 14K to 22K. Studies of in vitro phosphorylation with purified virions and with cells infected with a US9-defective HSV-1 mutant suggested that a tegment phosphoprotein encoded by the US9 gene may be a target of HSV-2 US3 protein kinase.
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PMID:Identification of a target protein of US3 protein kinase of herpes simplex virus type 2. 804 10

The Rho guanosine 5'-triphosphatase (GTPase) cycles between the active guanosine triphosphate (GTP)-bound form and the inactive guanosine diphosphate-bound form and regulates cell adhesion and cytokinesis, but how it exerts these actions is unknown. The yeast two-hybrid system was used to clone a complementary DNA for a protein (designated Rhophilin) that specifically bound to GTP-Rho. The Rho-binding domain of this protein has 40 percent identity with a putative regulatory domain of a protein kinase, PKN. PKN itself bound to GTP-Rho and was activated by this binding both in vitro and in vivo. This study indicates that a serine-threonine protein kinase is a Rho effector and presents an amino acid sequence motif for binding to GTP-Rho that may be shared by a family of Rho target proteins.
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PMID:Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho. 857 Nov 26

The critical pathways through which ionizing radiation induces malignant transformation and cell death are not well defined. Raf-1, a cytoplasmic serine-threonine protein kinase, mediates the transmission of mitogenic signals initiated at the cell membrane to the nucleus, resulting in the activation of transcription factors that regulate cell growth and proliferation. Moreover, Raf-1 overexpression and activation increases the survival response of mammalian cells to the toxic effects of ionizing radiation by an as-yet unknown mechanism (refs 3, 4 and V. Soldatenkov et al.; manuscript submitted). Somewhat analogous to mitogen-induced signalling, radiation stimulates protein-tyrosine kinase(s) and transcription factors. No direct biochemical link has been established, however, between radiation-stimulated protein tyrosine phosphorylation and downstream signals. Here we report a series of radiation-responsive events in which protein-tyrosine phosphorylation is followed by membrane recruitment, then tyrosine phosphorylation and activation of Raf-1 in vivo. Our results show that radiation-stimulated protein-tyrosine kinase(s) modify Raf-1, and implicate Raf-1 in the ionizing-radiation signal-transduction pathway.
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PMID:Activation of Raf by ionizing radiation. 875 75

The double-stranded DNA-activated protein kinase (DNA-PK) is a serine-threonine protein kinase that is composed of a large catalytic subunit (p350) and a DNA-binding protein of 70 and 80 kDa subunits known as the Ku autoantigen. When targeted to DNA by free DNA ends, DNA-PK phosphorylates many DNA-binding proteins and transcription factors. Previously, DNA-PK had only been purified and characterized from transformed human tissue culture cells. Here we report that DNA-PK is an abundant protein in human placenta and lymphocytes. We have purified the placental DNA-PK to homogeneity and show that its biochemical properties are similar to those of the HeLa cell enzyme.
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PMID:Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta. 903 91

Protein kinase CK2 (casein kinase II) is a serine-threonine protein kinase with many substrates, some of which are involved in cell cycle regulation. CK2 activity is elevated in human solid tumors and leukemia, and dysregulated expression of CK2 induces lymphoma in transgenic mice. Mice that are deficient in p53 also develop lymphomas, and p53 activity may be regulated by CK2 phosphorylation. Here we demonstrate that CK2alpha transgenic mice partially or completely deficient in p53 develop thymic lymphomas at a markedly accelerated rate when compared to p53-deficient mice lacking the transgene. Lymphomas originating from CK2alpha transgenic mice that are heterozygous for p53 generally lose the wild type p53 allele, indicating that loss of p53 is an important step in tumor progression. Moreover, though lymphomas occur as early as 3 weeks of age in the transgenic mice that are nullizygous for p53, they are still monoclonal, indicating that additional stochastic mutations are required for their development. These lymphomas express high levels of myc mRNA and frequently ectopically express Lmo-2, a transcription factor involved in human T cell acute lymphocytic leukemia. The p53-null CK2alpha transgenic lymphomas grow rapidly but are highly prone to apoptosis, suggesting that transformation occurs through synergistic dysregulation of cell cycle control induced by misexpression of CK2 and loss of function of p53.
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PMID:p53 deficiency and misexpression of protein kinase CK2alpha collaborate in the development of thymic lymphomas in mice. 966 28

U73122, a phospholipase C inhibitor, dose dependently blocks the cGMP-induced Ca2+ release in sea urchin eggs and homogenates. U73122 inhibition was prevented by cotreatment with dithiothreitol (DTT), but DTT is ineffective when eggs or homogenates were pretreated with U73122. U73122 action is different from the other sulfhydryl reagents, thimerosal and N-ethylmaleimide, which cause Ca2+ release in egg homogenates at high concentration, but at lower concentration have no significant effect on cGMP-induced Ca2+ release. Histone, a reported NAD glycohydrolase (NADase) activator, was found to induce Ca2+ release in egg homogenates via the same pathway as the cGMP response, since histone-induced Ca2+ release is blocked by Rp-8-pCPT-cGMPS, a cGMP-dependent protein kinase (PKG) inhibitor, and nicotinamide, a NADase inhibitor. Histone-induced Ca2+ release is similarly blocked by U73122. The aminosteroid U73122 does not inhibit cADPR-induced Ca2+ release, which is significantly reduced by PKG inhibitors. Furthermore, U73122 has no significant effect on phorbol 12-myristate 13-acetate induced-cytoplasmic alkalinization in intact eggs, which depends on protein kinase C activity. These results suggest that U73122 does not act as a general serine-threonine protein kinase inhibitor, and the aminosteroid inhibition of the cGMP-induced Ca2+ release may interfere with ADP ribosyl cyclase activity.
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PMID:U73122 blocked the cGMP-induced calcium release in sea urchin eggs. 966 30


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