Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the expression of p34cdc2 and its kinase activity in human gastric and colonic carcinoma cell lines and carcinoma tissues and studied its relation with a tumor-suppressor gene product, p53. All the gastric and colonic cancer cell lines expressed p34cdc2 and showed its kinase activity at various levels. When the cells were arrested in mitotic metaphase by the use of nocodazole, p34cdc2 kinase activity was induced and p53 was apparently phosphorylated. Of 12 gastric carcinoma cases, 11 (91.7%) showed higher p34cdc2 kinase activity in tumor tissues than in corresponding non-neoplastic mucosa. The protein kinase activities in the individual cases were well correlated with the levels of p34cdc2 protein expression. A good correlation was also found between the expression of p34cdc2 and proliferating cell nuclear antigen (PCNA). Almost all the colonic carcinomas showed higher cdc2 kinase activity and increased p34 expression when compared with non-neoplastic mucosa. Interestingly, most of the gastric and colonic carcinomas having high cdc2 kinase activity expressed high levels of p53. These findings suggest that the increased p34cdc2 kinase activity might cause the development and proliferation of gastric and colonic carcinomas, partly through abnormal p53 accumulation.
 ...
PMID:Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas. 841 2

Using ssDNA-cellulose column chromatography, a 34 kDa ribonucleoprotein (p34) has been purified from a 0.4 M KCl crude extract of spinach chloroplasts as an effective phosphate acceptor for casein kinase II (CK-II) in vitro. Monomeric and oligomeric CK-IIs were copurified with p34 by the column chromatography and the kinases were separated from p34 by means of Mono Q column chromatography. It was found that (i) the purified p34 (pI 4.9) was phosphorylated specifically by CK-II in vitro; and (ii) similar polypeptides, such as p35 (pI 4.7) and p39 (pI 4.9) in maize and p33 (pI 4.7) in liverwort, were detected as ssDNA-binding chloroplast proteins phosphorylated by CK-II in vitro. The findings suggest that (i) RNPs that function as phosphate acceptors for CK-II exist commonly in chloroplasts among plant cells; and (ii) the physiological activity of RNPs is regulated by their specific phosphorylation by CK-II in chloroplasts.
 ...
PMID:Chloroplast ribonucleoproteins (RNPs) as phosphate acceptors for casein kinase II: purification by ssDNA-cellulose column chromatography. 858 36

The gene coding for the large subunit of herpes simplex virus type 2 ribonucleotide reductase (RR) (ICP10) has a unique 5' terminal domain the product of which has a serine/threonine (Ser/Thr) protein kinase (PK) catalytic domain preceded by a transmembrane (TM) segment. Because ICP10 localizes on the cell surface and is internalized by the endocytic pathway like an activated growth factor receptor (Hunter et al., 1995, Virology 210, 345-360), we asked whether it is ligand-inducible in order to examine whether it has intrinsic transphosphorylating activity. We constructed a chimeric expression vector that contains the extracellular and TM domains of the epidermal growth factor receptor (EGFR) joined to the intracellular PK and RR domains of ICP10 (pCH5) and established constitutively expressing cell lines in NIH3T3 2.2 cells that do not express EGFR. The chimeric protein, designated p210 CH5, localized to the surface of these cells as determined by immunofluorescent staining with MAb EGFR, and it bound 125I-EGF.p210 CH5 coprecipitated with protein species p170, p120, p88, p60, p44, p34, and p25. EGF treatment activated the PK activity of p210 CH5, resulting in its autophosphorylation and the phosphorylation of the p120, p88, and p34 species. Immunoprecipitation/immunoblotting with anti-ras-GAP antibody and phosphoamino acid analysis indicated that p120 is ras-GAP and it is phosphorylated on Ser/Thr residues. The identities of the phosphorylated p88 and p34 are still unknown. The data indicate that when fused to a ligand-regulated extracellular domain (EGFR), the ICP10 PK auto- and transphosphorylating activities are ligand-inducible. These findings support the interpretation that the ICP10 PK activity is intrinsic and indicate that ras-GAP is one of its phosphorylation substrates.
 ...
PMID:The protein kinase activity of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) fused to the extracellular domain of the epidermal growth factor receptor is ligand-inducible. 861 Apr 33

In the preceding report (Ladner, R.D., McNulty, D.E., Carr, S.A., Roberts, G.D., and Caradonna, S.J. (1996) J. Biol. Chem. 271, 7745-7751), we identified two distinct isoforms of dUTPase in human cells. These isoforms are individually targeted to the nucleus (DUT-N) and mitochondria (DUT-M). The proteins are nearly identical, differing only in a short region of their amino termini. Despite the structural differences between these proteins, they retain identical affinities for dUTP (preceding article). In previous work, this laboratory demonstrated that dUTPase is posttranslationally phosphorylated on serine residue(s) (Lirette, R., and Caradonna, S. (1990) J. Cell. Biochem. 43, 339-353). To extend this work and determine if both isoforms of dUTPase are phosphorylated, a more in depth analysis of dUTPase phosphorylation was undertaken. [32P]Orthophosphate-labeled dUTPase was purified from HeLa cells, revealing that only the nuclear form of dUTPase is phosphorylated. Electrospray tandem mass spectrometry was used to identify the phosphorylation site as Ser-11 in the amino-terminal tryptic peptide PCSEETPAIpSPSKR (the NH2-terminal Met is removed in the mature protein). Mutation of Ser-11 by replacement with Ala blocks phosphorylation of dUTPase in vivo. Analysis of the wild type and Ser-11 --> Ala mutant indicates that phosphorylation does not regulate the enzymatic activity of the DUT-N protein in vitro. Additionally, experiments with the Ser-11 --> Ala mutant indicate that phosphorylation does not appear to play a role in subunit association of the nuclear form of dUTPase. The amino acid context of this phosphorylation site corresponds to the consensus target sequence for the cyclin-dependent protein kinase p34(cdc2). Recombinant DUT-N was specifically phosphorylated on Ser-11 in vitro with immunoprecipitated p34(cdc2). Together, these data suggest that the nuclear form of dUTPase may be a target for cyclin-dependent kinase phosphorylation in vivo.
 ...
PMID:Identification of a consensus cyclin-dependent kinase phosphorylation site unique to the nuclear form of human deoxyuridine triphosphate nucleotidohydrolase. 863 17

Transcription factor IIH (TFIIH) is a multisubunit protein complex essential for both the initiation of RNA polymerase class II (pol II)-catalyzed transcription and nucleotide excision repair of DNA. Recent studies have shown that TFIIH copurifies with the cyclin-dependent kinase (cdk)-activating kinase complex (CAK) that includes cdk7, cyclin H, and p36/MAT1. Here we report the isolation of two TFIIH-related complexes: TFIIH* and ERCC2/CAK. TFIIH* consists of a subset of the TFIIH complex proteins including ERCC3 (XPB), p62, p44, p41, and p34 but is devoid of detectable levels of ERCC2 (XPD) and CAK. ERCC2/CAK was isolated as a complex that exhibits CAK activity that cosediments with the three CAK components (cdk7, cyclin H, and p36/MAT1) as well as the ERCC2 (XPD) protein. TFIIH* can support pol II-catalyzed transcription in vitro with lower efficiency compared with TFIIH. This TFIIH*-dependent transcription reaction was stimulated by ERCC2/CAK. The ERCC2/CAK and TFIIH* complexes are each active in DNA repair as shown by their ability to complement extracts prepared from ERCC2 (XPD)- and ERCC3 (XPB)-deficient cells, respectively, in supporting the excision of DNA containing a cholesterol lesion. These data suggest that TFIIH* and ERCC2/CAK interact to form the TFIIH holoenzyme capable of efficiently assembling the pol II transcription initiation complex and directly participating in excision repair reactions.
 ...
PMID:Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH. 869 41

Protein phosphorylation by members of the Cdk (cyclin-dependent kinase) family of protein kinases is necessary for progression through the cell cycle. However, the primary sequence determinants of Cdk substrate specificity have yet to be examined quantitatively. We have used a panel of glutathione S-transferase peptide fusions to investigate the fine-structure specificity of p33(cdk2) and p34(cdc2). Our data indicate that the generally held consensus sequences for p34(cdc2) represent a significant oversimplification of its true specificity and that this specificity is conserved between species. p33(cdk2) and p34(cdc2) have similar but distinct substrate specificities that are affected modestly by the associated cyclin subunit. We derive specific values of phosphorylation efficiencies by these enzymes that can be used to estimate the phosphorylation potential of proposed Cdk substrates.
 ...
PMID:A predictive scale for evaluating cyclin-dependent kinase substrates. A comparison of p34cdc2 and p33cdk2. 881 Feb 85

EBNA-LP is a viral nuclear oncoprotein implicated in the immortalization of B lymphocytes by Epstein-Barr virus. An analysis of EBNA-LP migration on polyacrylamide gels was performed with protein derived from the X50-7 lymphoblastoid cell line blocked by hydroxyurea or aphidicolin at the G1/S phase of the cell cycle or by nocodazole at the G2/M phase. More slowly migrating species of EBNA-LP were detected in G2/M phase-arrested cell extracts. Release from nocodazole G2/M block or treatment with phosphatase caused the more slowly migrating species of EBNA-LP to disappear. Analyses of 32PO(4)(3-)-labeled EBNA-LP protein immunoprecipitated from the drug-synchronized cells showed that phosphorylated EBNA-LP was present throughout the cell cycle but that phosphorylation increased in G2 and was maximal at G2/M. Phosphoamino acid analysis revealed that all phosphorylation was on serine residues only. The ability of EBNA-LP to be phosphorylated by p34(cdc2) kinase and casein kinase II exclusively on serines implicates these enzymes as being potentially involved in EBNA-LP phosphorylation.
 ...
PMID:Cell cycle stage-specific phosphorylation of the Epstein-Barr virus immortalization protein EBNA-LP. 889 11

The enzyme N-myristoyl transferase transfers the 14 carbon fatty acid myristate to an N-terminal glycine residue in a small subset of cytoplasmic proteins. Many myristoyl proteins are components of cellular signalling pathways, some of which play important roles during embryonic development, for example protein kinase A. Thus, the function of N-myristoyl transferase is probably essential for embryogenesis and it is of some interest to study the enzyme in an organism with well understood developmental biology. In this paper we report the purification of a processed form of the Drosophila enzyme from peripheral membrane fractions of embryos by affinity chromatography to a protein containing leucine rich repeats. We have also isolated the Drosophila N-myristoyl transferase gene and determined its nucleotide sequence. The predicted amino acid sequence of the Drosophila enzyme is closely related to that of mammalian and fungal N-myristoyl transferases and residues essential for enzyme function are conserved. Our findings indicate that a fraction of Drosophila NMT is bound to the membrane and they are consistent with recent results for the human enzyme. We suggest that N-myristoyl transferase may be recruited to the membrane as part of a translational complex, perhaps by binding to p34 ribosome binding protein, a leucine rich repeat receptor of the microsomal membranes. We have also studied the expression pattern of the gene in the embryo by northern blot analysis and in situ hybridization. The transcripts appear to be uniformly distributed in the pre-cellular embryo but at later stages the RNA is barely detectable with these methods. However, from about stage 14, high levels of transcript are detected in a small number of randomly distributed cells of the central and peripheral nervous system.
 ...
PMID:Sequence and expression of Drosophila myristoyl-CoA: protein N-myristoyl transferase: evidence for proteolytic processing and membrane localisation. 904 45

The lamin B receptor (LBR) is an integral protein of the inner nuclear membrane that is modified at interphase by a nuclear envelope-bound protein kinase. This enzyme (RS kinase) specifically phosphorylates arginine-serine dipeptide motifs located at the NH2-terminal domain of LBR and regulates its interactions with other nuclear envelope proteins. To compare the phosphorylation state of LBR during interphase and mitosis, we performed phosphopeptide mapping of in vitro and in vivo 32P-labeled LBR and analyzed a series of recombinant proteins and synthetic peptides. Our results show that LBR undergoes two types of mitotic phosphorylation mediated by the RS and the p34(cdc2) protein kinases, respectively. The RS kinase modifies similar sites at interphase and mitosis (i.e. Ser76, Ser78, Ser80, Ser82, Ser84), whereas p34(cdc2) mainly phosphorylates Ser71. These findings clarify the phosphorylation state of LBR during the cell cycle and provide new information for understanding the mechanisms responsible for nuclear envelope assembly and disassembly.
 ...
PMID:Mitotic phosphorylation of the lamin B receptor by a serine/arginine kinase and p34(cdc2). 904 35

The nucleolar protein gar2 of fission yeast is structurally related to the multifunctional nucleolar protein nucleolin from vertebrates and has been shown to be implicated in production of 18S rRNA. gar2 contains several potential casein kinase 2 (CK2) phosphorylation sites and a single putative p34(cdc2 )phosphorylation site in the consensus S50PKK. Here, we show that, like nucleolin, gar2 is phosphorylated in vitro by both highly purified CK2 from CHO cells and p34(cdc2 )from starfish oocytes. Moreover, the substitution of alanine for the N-terminal serine 50 abolishes phosphorylation by p34(cdc2 )in vitro. We also provide evidence that gar2 is phosphorylated in vitro by a p13(suc1)-Sepharose-bound kinase from Schizosaccharomyces pombe extracts that displays cell cycle-regulated activity similar to that of the p34(cdc2(kinase. In vivo 32P labeling of cells indicates that gar2 is a phosphoprotein and that incorporation of phosphate on residue 50 occurs specifically at mitosis. Taken together, these results lead us to propose that gar2 is likely to be an in vivo substrate for the mitotic p34(cdc2 )kinase. However, this posttranslational modification of the gar2 protein does not appear to be essential for normal production of 18S rRNA.
 ...
PMID:Mitosis-specific phosphorylation of gar2, a fission yeast nucleolar protein structurally related to nucleolin. 921 81


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