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)

We and others have reported an association between raf-1 protein serine/threonine kinase activity and transformation of mammalian cells. Because constitutive tyrosine phosphorylation of specific polypeptides is, in general, indicative of the transformed state of cells, we investigated the effect of activation of raf-1 on phosphotyrosine-containing proteins in a human head and neck squamous cell carcinoma-derived cell line, PCI-06A. raf-1 expression and activity were modulated in PCI-06A cells by means of stable DNA transfection of either the entire coding domain of the human c-raf-1 cDNA (in the sense or antisense orientation) or a fragment of c-raf-1 cDNA coding for the kinase domain of raf-1. Our data showed that constitutive activation of raf-1 correlated with morphological transformation, whereas the inhibition of raf-1 expression and activity had no detectable effect on cell morphology as compared with the untransfected cells. Immunoprecipitation of whole-cell lysates with anti-phosphotyrosine antibody followed by anti-phosphotyrosine immunoblotting revealed four phosphotyrosine-containing proteins of approximately 129, 120, 110, and 63 kDa (I-IV, respectively) in the antisense c-raf-1 cDNA-transfected cells showing relatively diminished raf-1 activity but not in the transfectants expressing activated raf. We concluded that tyrosine phosphorylation of I-IV proteins is abrogated in PCI-06A squamous carcinoma cells transformed with constitutively active raf-1 protein kinase.
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PMID:Correlation of constitutive activation of raf-1 with morphological transformation and abrogation of tyrosine phosphorylation of distinct sets of proteins in human squamous carcinoma cells. 902 7

Protein kinase CK2, formerly known as casein kinase II, is a ubiquitous protein serine/threonine kinase. The enzyme exists in tetrameric complexes composed of two catalytic (CK2 alpha and/or CK2 alpha') subunits and two subunits (CK2 beta) that appear to have a role in modulating the activity of the catalytic subunits. With the exception of their unrelated carboxy-terminal domains, the two isozymic forms of mammalian CK2 display extensive sequence identity. Furthermore, CK2 alpha and CK2 alpha' exhibit remarkable conservation between species, suggesting that they may have unique functions. In the present study, the cDNAs encoding CK2 alpha and CK2 alpha' were modified by addition of the hemagglutinin tag of the influenza virus at the amino terminus of the respective proteins. The epitope-tagged proteins were transfected into Cos-7 cells and the localization of the expressed proteins determined by indirect immunofluorescence using monoclonal antibodies specific for the epitope tag. The use of transfection favors the formation of homotetrameric complexes (i.e., alpha 2 beta 2, alpha' 2 beta 2) instead of heterotetrameric complexes (i.e., alpha alpha' beta 2) that are present in many cells. Epitope-tagged CK2 alpha and CK2 alpha' displayed kinase activity and the ability to form complexes with CK2 beta. The results of these studies also indicate definitively that CK2 alpha and CK2 alpha' are both localized predominantly within the nucleus. Mutation of conserved lysine residues within the ATP binding domains of CK2 alpha and CK2 alpha' resulted in loss of kinase activity. However, examination of these mutants indicates that kinase activity is not essential for formation of complexes between subunits of CK2 and is not required for nuclear localization of CK2.
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PMID:Expression and localization of epitope-tagged protein kinase CK2. 909 2

We identified a novel Drosophila gene, Dpkn (Drosophila protein kinase related to PKN), encoding a putative protein serine/threonine kinase. Although the cDNA obtained was incomplete at its 5'-terminal region, the deduced amino acid sequence of its kinase domain exhibits a high degree of similarity to protein kinase N (PKN), which has a kinase domain related to protein kinase C (PKC) and leucine zipper-like sequences in the amino terminal region. Expression of Dpkn was observed throughout Drosophila development, although its expression level decreased at later stages of embryogenesis. The expression of Dpkn is first detected in the newly formed mesodermal cell layer and is then restricted to the developing somatic musculature, indicating a possible role of Dpkn in the development of somatic muscles in Drosophila.
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PMID:Identification of a novel Drosophila protein kinase highly homologous to protein kinase N (PKN). 912 15

DNA amplification on chromosome 20q13 is commonly detected in breast cancer and correlates with poor prognosis. Definitive critical target genes on this amplicon have however, not yet been identified. We describe in this paper isolation of a novel gene named BTAK, encoding a putative member of protein serine/threonine kinase family localized on chromosome 20q13 that is amplified and overexpressed in breast tumor cell lines. BTAK maps close to the critical region of amplification defined earlier on this amplicon. Deduced amino acid sequence shows conservation of all the subdomains predicted in protein kinase super family. Translated BTAK peptide shows significant homology with previously cloned protein serine/threonine kinase encoding genes Ip11 from S cerevisae and aurora from Drosophila, both shown to be functionally involved in normal chromosome segregation process. Our findings suggest that amplification and overexpression of BTAK may be playing a critical role in oncogenic transformation of breast tumor cells.
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PMID:A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. 917 55

Raf-1 protein serine/threonine kinase has been implicated in growth and damage-responsive signal transduction pathways. Several reports indicate an important role of Ras protein in the growth factor-induced activation of Raf-1. Here we investigated the possible involvement of Ras in ionizing radiation-induced activation of Raf-1. Irradiation of MDA-MB 231 human breast cancer cells caused an increase in GTP-binding and hydrolysis on Ras, and co-immunoprecipitations of endogenous Grb2 with Sos and Raf-1 with Ras. An increase in the level of membrane-bound Raf-1, and tyrosine-phosphorylation of Raf-1 were observed after irradiation. Consistent with these changes, irradiation of cells stimulated the catalytic activity of Raf-1. Finally, radiation treatment of breast cancer cells led to an increase in the phosphorylation and activity of the mitogen-activated protein kinase. Based on these biochemical modifications in vivo, we conclude that Raf-1 functions as an effector of Ras in the radiation-responsive signal transduction pathway leading to the activities of Raf-1 and mitogen-activated protein kinase.
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PMID:Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast cancer cells. 923 77

Human prk encodes a novel protein serine/threonine kinase capable of strongly phosphorylating casein but not histone H1 in vitro. prk expression is tightly regulated at various levels during different stages of the cell cycle in lung fibroblasts. The Prk kinase activity is relatively low during mitosis, G1, and G1/S, and peaks during late S and G2 stages of the cell cycle. Recombinant human Prk expressed through the baculoviral vector system is capable of phosphorylating Cdc25C, a positive regulator for the G2/M transition. Human prk shares significant sequence homology with Saccharomyces cerevisiae CDC5 and Drosophila melanogaster polo, both of which are essential for mitosis and meiosis. Full-length prk transcripts greatly potentiate progesterone-induced meiotic maturation of Xenopus laevis oocytes. On the other hand, antisense prk transcripts significantly delay and reduce the rate of oocyte maturation. When expressed in a CDC5 mutant strain of S. cerevisiae, human Prk, but not a deletional mutant protein, fully rescues the temperature-sensitive phenotype of the budding yeast. Taken together, prk may represent a new protein kinase, playing an important role in regulating the onset and/or progression of mitosis in mammalian cells.
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PMID:Human Prk is a conserved protein serine/threonine kinase involved in regulating M phase functions. 935 31

Protein kinase CKII (CKII) is a ubiquitous protein serine/threonine kinase. CKII usually exists in tetrameric complexes composed of two catalytic (CKII alpha and/or CKII alpha') and two regulatory (CKII beta) subunits. In the present study, using a combined in vivo and in vitro approach, we have investigated the role of CKII subunits in the formation of the tetrameric structure of CKII and the formation of the polymeric structure of CKII holoenzyme. Our in vivo experiments show that CKII beta interacts with either another CKII beta or CKII alpha and that CKII alpha does not interact with another CKII alpha (or CKII alpha'). Our in vitro experiments also show that CKII beta is able to associate with both CKII alpha and another CKII beta and that CKII alpha exists as a monomeric form in solution. These data indicate that CKII beta mediates the formation of a tetramer by both the dimerization of CKII beta and the interaction of CKII beta with CKII alpha. The results of this study also suggest that CKII beta may be involved in the formation of the polymeric structure of the CKII holoenzyme.
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PMID:Characterization of protein interaction among subunits of protein kinase CKII in vivo and in vitro. 957 30

Maternally localized cytoplasmic determinants play important roles in the embryogenesis of many animals, including ascidians. Cytoplasmic determinants are particularly important in the determination of cell fates, and in the establishment of the embryonic axes. Ascidians, which show mosaic development, are good models for the study of maternal cytoplasmic determinants. Here we report the isolation and characterization of HrPOPK-1 (Halocynthia roretzi posterior protein kinase-1), a putative protein serine/threonine kinase. HrPOPK-1 cDNA was obtained from a Halocynthia roretzi fertilized egg cDNA library by screening for localized RNAs using whole-mount in situ hybridization. HrPOPK-1 mRNA is strongly localized at the posterior pole of embryos. The pattern of HrPOPK-1 mRNA localization during early embryogenesis is identical to that of HrWnt-5 in Halocynthia roretzi, and to those of the posterior end mark (pem) transcripts of Ciona savignyi. In addition, HrPOPK-1 shows zygotic expression in neural tissues at the tailbud stage. These results show that the temporal regulation of HrPOPK-1 transcription is complex.
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PMID:Maternally localized RNA encoding a serine/threonine protein kinase in the ascidian, Halocynthia roretzi. 976 57

Gene expression is necessary for the formation and consolidation of long term memory in both invertebrates and vertebrates. Here, we describe the expression and characterization of candidate plasticity gene 16 (cpg16), a protein serine/threonine kinase that was previously isolated from rat hippocampus as a plasticity-related gene. CPG16, when expressed in and purified from bacteria and COS7 cells, was only capable of autophosphorylation and phosphorylation of myelin basic protein but failed to phosphorylate many other peptides and proteins in in vitro phosphorylation assays. Recombinant CPG16, when overexpressed and purified from COS7 cells, had a relatively low level of autophosphorylation activity. This activity was significantly stimulated when cAMP-elevating agents (forskolin, 8-bromo-cAMP) were added to the cells but not by any other extracellular stimuli tested, e.g. serum, phorbol esters, and a calcium ionophore. Although the stimulation of CPG16 activity was inhibited by the cAMP-dependent protein kinase inhibitor H-89, it did not serve as a direct substrate for this kinase. This suggests that CPG16 may be activated by a cAMP-stimulated protein kinase cascade. Immunolocalization studies in COS7 and NIH-3T3 cells showed mostly cytoplasmic localization of CPG16 that turned partially nuclear upon stimulation with 8-bromo-cAMP. Moreover, overexpression of CPG16 seems to partially inhibit cAMP-stimulated activity of the transcription factor CREB (cAMP response element-binding protein), suggesting its involvement in the down-regulation of cAMP-induced transcription. Thus, CPG16 is a protein serine/threonine kinase that may be involved in a novel signaling pathway downstream of cAMP-dependent protein kinase.
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PMID:CPG16, a novel protein serine/threonine kinase downstream of cAMP-dependent protein kinase. 991 91

The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an enormous, 470-kDa protein serine/threonine kinase that has homology with members of the phosphatidylinositol (PI) 3-kinase superfamily. This protein contributes to the repair of DNA double-strand breaks (DSBs) by assembling broken ends of DNA molecules in combination with the DNA-binding factors Ku70 and Ku80. It may also serve as a molecular scaffold for recruiting DNA repair factors to DNA strand breaks. This study attempts to better define the role of protein kinase activity in the repair of DNA DSBs. We constructed a contiguous 14-kb human DNA-PKcs cDNA and demonstrated that it can complement the DNA DSB repair defects of two mutant cell lines known to be deficient in DNA-PKcs (M059J and V3). We then created deletion and site-directed mutations within the conserved PI 3-kinase domain of the DNA-PKcs gene to test the importance of protein kinase activity for DSB rejoining. These DNA-PKcs mutant constructs are able to express the protein but fail to complement the DNA DSB or V(D)J recombination defects of DNA-PKcs mutant cells. These results indicate that the protein kinase activity of DNA-PKcs is essential for the rejoining of DNA DSBs in mammalian cells. We have also determined a model structure for the DNA-PKcs kinase domain based on comparisons to the crystallographic structure of a cyclic AMP-dependent protein kinase. This structure gives some insight into which amino acid residues are crucial for the kinase activity in DNA-PKcs.
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PMID:Requirement for the kinase activity of human DNA-dependent protein kinase catalytic subunit in DNA strand break rejoining. 1020 11


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