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)

The Saccharomyces cerevisiae SIP3 gene was identified in a two-hybrid screen for proteins that interact in vivo with the SNF1 protein kinase, which is necessary for release of glucose repression. We showed that the C-terminal part of SIP3, recovered through its ability to interact with SNF1, strongly activates transcription when tethered to DNA. We have cloned and sequenced the entire SIP3 gene. The predicted 142-kD SIP3 protein contains a putative leucine zipper motif located in its C terminus. The native SIP3 protein also interacts with DNA-bound SNF1 and activates transcription of a target gene. A complete deletion of the SIP3 gene did not confer phenotypes characteristic of snf1 mutants. However, in a mutant deficient for the SNF1 kinase activity due to loss of the SNF4 stimulatory function, increased dosage of SIP3 partially restored expression of the glucose-repressible SUC2 gene. Overexpression of the C terminus of SIP3 caused defects in growth and SUC2 expression which were remedied by overexpressing SNF1. Taken together, these genetic data suggest that SIP3 is functionally related to the SNF1 protein kinase pathway.
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PMID:Analysis of the SIP3 protein identified in a two-hybrid screen for interaction with the SNF1 protein kinase. 812 9

A novel protein kinase, designated PKN, was identified by molecular cloning from a human hippocampus cDNA library. PKN consists of 942 amino acids with a calculated molecular mass of 103,925 daltons. PKN has leucine zipper-like sequences in its amino terminal region and contains a catalytic domain that shows strong similarity to that of protein kinase C family. Northern blot analysis indicates PKN is expressed ubiquitously in human tissues. Antisera against PKN identified a 120K dalton protein on SDS polyacrylamide gel electrophoresis when PKN was expressed in the insect cells or COS7 cells. Recombinant PKN revealed an intrinsic protein kinase activity associated with a 120K protein. This activity was abolished by mutation of the lysine residue in the potential ATP binding site.
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PMID:A novel protein kinase with leucine zipper-like sequences: its catalytic domain is highly homologous to that of protein kinase C. 813 37

Activating transcription factor-3 (ATF-3) is one member of a large family of leucine zipper transcription factors which bind to promoters responsive to cAMP and phorbol ester at the related cAMP (CRE) and phorbol ester response elements. We report here that ATF-3 is coexpressed with the neuropeptide precursor proenkephalin in human neuroblastoma SK-N-MC cells. Cotransfection experiments indicate that activation of proenkephalin gene expression by ATF-3 is dependent upon both the catalytic subunit of the cAMP-dependent protein kinase and the CRE-2 element. The CRE-2 element is essential for second messenger-inducible expression and is known to bind AP-1-like transcription factors. ATF-3 expressed in bacteria or from rabbit reticulocyte lysates binds to the proenkephalin CRE-2 element as a homodimer and as a heterodimer with Jun-D, another activator of proenkephalin transcription. ATF-3 stimulates binding of Jun-D to the proenkephalin CRE-2 element and acts synergistically with Jun-D to induce proenkephalin gene expression. Sequential immunoprecipitations of ATF-3 from SK-N-MC cells expressing proenkephalin indicate that ATF-3 is complexed with Jun-D in vivo and that both proteins are highly phosphorylated. Together, our results suggest that ATF-3 may play an important role in the regulation of gene expression by cAMP-dependent intracellular signaling pathways.
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PMID:Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression. 815 31

We have identified a novel protein kinase, designated MLK-3, from human thymus using RT-PCR and cDNA library screening. The deduced open reading frame, derived from sequencing a 3.5 kb MLK-3 cDNA, encodes a protein of 847 amino acids with several interesting structural features. These include an SH3 domain in the absence of an SH2 domain, a region containing two leucine zippers with an adjacent carboxy-terminal basic region, and a proline rich region. This kinase shows homology with the mixed-lineage family of protein kinases (MLK) and shares the unusual leucine zipper-basic motif found in previously identified MLK kinases. By northern analysis, MLK-3 mRNA was detected in a wide variety of normal and transformed human cell lines and tissue specimens. The gene encoding MLK-3 has been mapped using fluorescence in situ hybridization to human chromosome 11 q13.1-13.3, a region frequently altered in human malignancies.
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PMID:MLK-3: identification of a widely-expressed protein kinase bearing an SH3 domain and a leucine zipper-basic region domain. 818 72

The recent identification of Max, a nuclear phosphoprotein that dimerizes with members of the Myc protein family, has provided an additional tool to examine the role of the Myc oncoprotein as a sequence-specific DNA binding protein and a potential regulator of gene transcription. Here we report the nucleotide sequence of an avian max gene isolated from a lambda EMBL3 genomic library prepared from size-selected chicken embryo fibroblast DNA. The complete transcription unit encoding chicken Max is contained on a 5.7 kbp BglII DNA fragment which expresses an appropriately sized max mRNA of 1.5 kb following transfection of C3H10T1/2 mouse fibroblasts. The coding region of the chicken max gene is organized into five exons and the overall identity between the human and chicken max coding sequences is 85% at the nucleotide level and 96% at the amino acid level. The basic helix-loop-helix/leucine zipper region, the casein kinase II phosphorylation sites and the nuclear localization signal sequence are 100% conserved in all vertebrate Max proteins characterized to date. DNA sequence analysis of the 5' flanking region of the chicken max coding sequence reveals the absence of consensus TATA or CAAT motifs, but the presence of numerous GC-rich sequences that are typical in eukaryotic genes which are expressed constitutively in different tissues and under different growth conditions.
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PMID:Structural analysis of the chicken max gene. 829 Feb 77

We have cloned and sequenced a cDNA coding for rice elongation factor 1 beta (EF-1 beta). The clone was 1420 bp long and contained an open reading frame coding for 229 amino acids. The overall identity between rice EF-1 beta and rice EF-1 beta' [Matsumoto, S., Oizumi, N., Taira, H. and Ejiri, S. (1992) FEBS Lett. 311, 46-48] is 60% at the amino acid sequence level; a higher percent identical residues (81%) were especially observed in the C-terminal region. Rice EF-1 beta has no conserved phosphorylation site for casein kinase II and no leucine zipper motif, although these motifs are well conserved in EF-1 delta (= beta in plants) subunits of animal EF-1.
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PMID:Cloning and characterization of the cDNA encoding rice elongation factor 1 beta. 830 47

N-myc is amplified between 5 and several hundred-fold frequently in neuroblastomas and, at lower frequency, in other human cancers with neuronal qualities, including retinoblastomas, gliomas, astrocytomas and small cell lung cancers. In neuroblastomas N-myc amplification is significantly correlated with poor prognosis; for other types of tumors such a correlation is difficult to make, due to low incidence of amplification. Amplification is associated with elevated expression, both of mRNA and protein. N-myc encodes two polypeptides of relative masses of 62 and 64 kDa, which are phosphorylated, at least in vitro, by casein kinase II and that are localized in the nucleus. There they can associate in vivo with another protein, Max, through a C-terminal dimerization motif, the leucine zipper. An N-terminal portion of N-myc, referred to as 'Myc-boxes', can substitute for the transcription-activating function of the yeast transcription factor Gal 4, thus raising the possibility that N-myc itself may act as a transcription factor, either alone or in association with other factors.
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PMID:Amplification of N-myc as a prognostic marker for patients with neuroblastoma. 844 74

Protein kinases play pivotal roles in the control of many cellular processes. In a search for protein kinases expressed in human epithelial tumour cells, we discovered two members of a novel protein kinase family [Dorow, D. S., Devereux, L., Dietzsch, E. & de Kretser, T. A. (1993) Eur. J. Biochem. 213, 701-710]. Due to the unique mixture of structural domains within their amino acid sequences, we named the family mixed-lineage kinases (MLK). We initially isolated clones encoding partial cDNAs of MLK1 and 2 from a human colonic cDNA library. The MLK2 cDNA was subsequently used to screen a human brain cDNA library and we have now cloned and sequenced a 3454-bp cDNA encoding the full-length MLK2 protein. The predicted MLK2 polypeptide has 954 amino acids and contains a src homology 3 (SH3) domain, a kinase catalytic domain, a double leucine zipper and basic domain, and a large C-terminal domain. The 22-amino-acid N-terminal region has four glutamic acid residues immediately following the initiator methionine. Beginning at amino acid 23, the 55-amino-acid SH3 domain contains a 5-amino-acid insert in a position corresponding to inserts of 6 and 15 residues in the SH3 domains of n-src and the phosphatidylinositol 3'-kinase. Adjacent to the SH3 domain is a kinase catalytic domain with conserved motifs associated with both serine/threonine and tyrosine specificity. Beginning nine residues C-terminal to the catalytic domain, there are two leucine/isoleucine zippers separated by a 13-amino-acid spacer sequence and followed by a stretch of basic residues. The polybasic sequence contains a motif that is similar to nuclear localisation signals from several proteins. The C-terminal domain is composed of 491 amino acids of which 17% are serine or threonine and 16% are proline. This domain also has a biased ratio of basic to acidic amino acids with a calculated pI of 9.38. When used as a probe to examine mRNA expression in human tissues, a MLK2 cDNA hybridised to a species of 3.8 kb that was expressed at highest levels in RNA from brain and skeletal muscle. The 3454-bp cDNA was also used for fluorescence in situ hybridisation to localise the MLK2 gene to human chromosome 19 q13.2.
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PMID:Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2. 853 94

The gene coding for phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) is expressed in all gluconeogenic tissues, but stimulation of its rate of transcription by cAMP is robust only in liver. Evidence has accumulated which suggests that a liver-enriched transcription factor, likely a member of the CCAAT/enhancer binding protein (C/EBP) family, is required along with other ubiquitously expressed transcription factors to mediate this liver-specific response to cAMP. In this study, we examined the ability of C/EBP to participate in the cAMP-mediated activation of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription in hepatoma cells. Expression of a dominant repressor of C/EBP in hepatoma cells significantly inhibited the protein kinase A-stimulated transcription of the PEPCK promoter, suggesting that a C/EBP family member was required for maximal transcriptional activation by protein kinase A. To provide additional support for this hypothesis, we prepared GAL4 fusion proteins containing C/EBP domains. Both C/EBPalpha and C/EBPbeta GAL4 fusion proteins were capable of stimulating transcription from promoters containing binding sites for the DNA-binding domain of GAL4. However, only the GAL4-C/EBPalpha fusion protein demonstrated the ability to synergize with the other transcription factors bound to the PEPCK promoter which are required to mediate cAMP responsiveness. The DNA-binding domain of C/EBPalpha was not required for this activity in hepatoma cells, although in non-hepatoma cells the basic region leucine zipper domain appeared to inhibit the ability of C/EBPalpha to participate in mediating cAMP responsiveness. These results suggest that the liver-specific nature of the cAMP responsiveness of the PEPCK promoter involves the recruitment of C/EBPalpha to the cAMP response unit.
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PMID:The alpha-isoform of the CCAAT/enhancer-binding protein is required for mediating cAMP responsiveness of the phosphoenolpyruvate carboxykinase promoter in hepatoma cells. 862 91

The SNF1 protein kinase has been widely conserved in plants and mammals. In Saccharomyces cerevisiae, SNF1 is essential for expression of glucose-repressed genes in response to glucose deprivation. Previous studies supported a role for SNF1 in relieving transcriptional repression. Here, we report evidence that SNF1 modulates function of a transcriptional activator, SIP4, which was identified in a two-hybrid screen for interaction with SNF1. The N terminus of the predicted 96-kDa SIP4 protein is homologous to the DNA-binding domain of the GAL4 family of transcriptional activators, with a C6 zinc cluster adjacent to a coiled-coil motif The C terminus contains a leucine zipper motif and an acidic region. When bound to DNA, a LexA-SIP4 fusion activates transcription of a reporter gene. Transcriptional activation by SIP4 is regulated by glucose and depends on the SNF1 protein kinase. Moreover, SIP4 is differentially phosphorylated in response to glucose availability, and phosphorylation requires SNF1. These findings suggest that the SNF1 kinase interacts with a transcriptional activator to modulate its activity and provide the first direct evidence for a role of SNF1 in activating transcription in response to glucose limitation.
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PMID:Yeast SNF1 protein kinase interacts with SIP4, a C6 zinc cluster transcriptional activator: a new role for SNF1 in the glucose response. 862 58


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