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)

During neurogenesis in Drosophila, groups of equipotential, neurally competent cells choose between epidermal and neural fates. Notch, a phylogenetically conserved transmembrane protein, may act as a receptor in a lateral signalling pathway in which a single neural precursor is chosen from each group and the neural fate of the other cells is inhibited, causing them to differentiate into epidermis. Possible intracellular transduction events mediating signals from Notch are, however, unknown. shaggy is also required for the lateral signal and encodes serine/threonine protein kinases with homology to the glycogen synthase kinase-3 (GSK-3) enzymes that act in signal transduction pathways in vertebrates. We report here that, in transgenic flies, GSK-3 beta can substitute for shaggy, and we also present a study of epistatic relationships between shaggy and gain and loss of function alleles of Notch. The results indicate that shaggy/GSK-3 is part of a signalling pathway downstream of Notch.
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PMID:Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. 838 71

The v-mpl oncogene transduced in the myeloproliferative leukemia virus (MPLV) encodes a truncated form of a putative receptor protein that belongs to the cytokine receptor superfamily. We previously reported the cloning of complete human c-MPL cDNA. In the present report, we show that the murine Mpl proto-oncogene is located at the D-band of murine chromosome 4, in a region in synteny with human chromosome 1p34, where MPL was previously located. RNA blot analysis of murine hematopoietic tissues and cells lines indicated that Mpl is expressed in immature hematopoietic precursor cells. Molecular cloning of murine proto-oncogene c-Mpl cDNAs is also reported. Two cDNA species were isolated. One potentially encodes a transmembrane protein. The extracellular domain of this protein has two repeats of the cytokine receptor domain common to all members of this receptor family. The cytoplasmic domain has no protein kinase or phosphatase motifs, but does contain a sequence that has been shown to be essential for the transmission of a growth signal in several other members of the family. Comparison of murine and human putative proteins indicated that they shared 81% amino acid identity, the most conserved region being the cytoplasmic domain (91% identity). The other Mpl cDNA clones potentially encode a soluble form of this receptor chain. A chimeric receptor containing the extracellular domain of the granulocyte colony-stimulating factor (G-CSF) receptor fused to the transmembrane and cytoplasmic domains of Mpl was able to induce G-CSF responsiveness when transfected into the interleukin 3 (IL-3)-dependent cell line BAF/BO3. This demonstrated that the cytoplasmic Mpl domain is most probably implicated in proliferative signal transduction.
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PMID:Characterization of the murine Mpl proto-oncogene, a member of the hematopoietic cytokine receptor family: molecular cloning, chromosomal location and evidence for a function in cell growth. 839 66

GPI-anchored surface proteins mediate many important functions, including transport, signal transduction, adhesion, and protection against complement. They cluster into glycolipid-based membrane domains and caveolae, plasmalemmal vesicles involved in the transcytosis and endocytosis of these surface proteins. However, in lymphocytes, neither the characteristic flask shaped caveolae nor caveolin, a transmembrane protein typical of caveolae, have been observed. Here, we show that the GPI-anchored CD59 molecule on Jurkat T cells is internalized after cross-linking, a process inhibited by nystatin, a sterol chelating agent. Clustered CD59 molecules mostly accumulate in non-coated invaginations of the lymphocyte membrane before endocytosis, in marked contrast with the pattern of CD3-TCR internalization. Cytochalasin H blocked CD59 internalization in lymphocytes, but neither CD3 internalization nor transferrin uptake. Confocal microscopy analysis of F-actin distribution within lymphocytes showed that CD59 clusters were associated with patches of polymerized actin. Also, we found that internalization of CD59 was prevented by the protein kinase C inhibitor staurosporine and by the protein kinase A activator forskolin. Thus, in lymphocytes, as in other cell types, glycolipid-based domains provide sites of integration of signaling pathways involved in GPI-anchored protein endocytosis. This process, which is regulated by both protein kinase C and A activity, is tightly controlled by the dynamic organization of actin cytoskeleton, and may be critical for polarized contacts of circulating cells.
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PMID:Endocytosis of GPI-anchored proteins in human lymphocytes: role of glycolipid-based domains, actin cytoskeleton, and protein kinases. 866 64

The cystic fibrosis transmembrane conductance regulator gene (CFTR) encodes a transmembrane protein (CFTR) which functions in part as a cyclic adenosine monophosphate (cAMP)-regulated chloride channel. CFTR expression is controlled temporally and cell specifically by mechanisms that are poorly understood. Insight into CFTR regulation could be facilitated by the successful introduction of the entire 230 kb human CFTR and adjacent sequences into mammalian cells. To this end, we have introduced two different CFTR-containing yeast artificial chromosomes (YACs) (320 and 620 kb) into Chinese hamster ovary-K1 (CHO) cells. Clonal cell lines containing human CFTR were identified by PCR, and the genetic and functional analyses of one clone containing each YAC are described. Integration of the human CFTR-containing YACs into the CHO genome at a unique site in each cell line was demonstrated by fluorescence in situ hybridization (FISH). Southern blot analysis suggested that on the order of one copy of human CFTR was integrated per CHO cell genome. Fiber-FISH and restriction analysis suggested that CFTR remained grossly intact. Northern analysis showed full-length, human CFTR mRNA. Immunoprecipitation followed by phosphorylation with protein kinase demonstrated mature, glycosylated CFTR. Finally, chloride secretion in response to cAMP indicated the functional nature of the human CFTR. This study provides several novel results including: (i) functional human CFTR can be expressed from these YACs; (ii) CHO cells are a permissive environment for expression of human CFTR; (iii) the level of human CFTR expression in CHO cells is unexpectedly high given the lack of endogenous CFTR production; and (iv) the suggestion by Fiber-FISH of CFTR integrity correlates with functional gene expression. These YACs and the cell lines derived from them should be useful tools for the study of CFTR expression.
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PMID:Functional human CFTR produced by stable Chinese hamster ovary cell lines derived using yeast artificial chromosomes. 900 71

The cystic fibrosis transmembrane conductance regulator (CFTR) is a transmembrane protein that is expressed in several epithelia, including kidney tubules. Mutations in CFTR (a PKA-chloride channel and/or regulator of other epithelial channels) give rise to the clinical manifestation of cystic fibrosis, and result in the synthesis of mutated proteins responsible for altering ion transport across secretory epithelia. The low abundance of endogenous CFTR makes a difficult to purify enough of the native protein to prepare anti-CFTR antibodies. We have used differential centrifugation to prepare cortical brush border membrane vesicles from pig kidney, cBBMV, and developed a method for the partial purification of CFTR. This is the first step in the isolation of native CFTR. The results show that CFTR is present in cBBMV. The purified protein will provide a clearer picture of the biophysical and biochemical properties of native CFTR.
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PMID:Partial purification of the pig kidney cystic fibrosis transmembrane regulator protein. 903 46

HIV-1 Nef protein shares a significant homology with the immunosuppressive and highly conserved retroviral transmembrane protein p15E. In the present study, extracellular Nef protein is shown to induce interleukin (IL)-10 mRNA expression in human peripheral blood mononuclear cells as well as in cells of H9 T and U937 promonocytic human cell lines. Release of IL-10 protein into supernatants of peripheral blood mononuclear cells stimulated with Nef is dose-dependent. Expression of cytokines IL-2, IL-4, IL-5, IL-12 p40, IL-13, and interferon gamma is not affected by Nef stimulation. IL-10 protein production induced by Nef is inhibited by the calcium/calmodulin phosphodiesterase inhibitor W-7 but not by the protein kinase A inhibitor H-89 nor the protein kinase C inhibitors staurosporine and calphostin C. The calcium chelating agent EGTA also inhibits the IL-10 production induced by Nef, and this inhibition is reversed by the addition of calcium along with Nef. These findings indicate that extracellular Nef may contribute to the immunopathogenesis of HIV infection by inducing IL-10.
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PMID:Interleukin 10 is induced by recombinant HIV-1 Nef protein involving the calcium/calmodulin-dependent phosphodiesterase signal transduction pathway. 909 66

The transmembrane protein CD5, expressed on all T cells and the B1 subset of B cells, modulates antigen receptor-mediated activation. We used the yeast two-hybrid system to identify proteins that interact with its cytoplasmic domain and play a role in CD5 proximal signaling events. We found that the beta subunit of the serine/threonine kinase casein kinase 2 (CK2) interacts specifically with the cytoplasmic domain of CD5. Co-immunoprecipitation experiments showed activation-independent association of CK2 with CD5 in human and murine B and T cell lines and murine splenocytes. The interaction of CK2 holoenzyme with CD5 is mediated by the amino terminus of the regulatory subunit beta. CK2 binds and phosphorylates CD5 at the CK2 motifs flanked by Ser459 and Ser461. Cross-linking of CD5 leads to the activation of CD5-associated CK2 in a murine B-lymphoma cell line and a human T-leukemia cell line and is independent of net recruitment of CK2 to CD5. In contrast, CK2 is not activated following cross-linking of the B cell receptor complex or the T cell receptor complex. This direct regulation of CK2 by a cell surface receptor provides a novel pathway for control of cell activation that could play a significant role in regulation of CD5-dependent antigen receptor activation in T and B cells.
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PMID:Regulation of casein kinase 2 by direct interaction with cell surface receptor CD5. 966 5

Bacteria live in capricious environments, in which they must continuously sense external conditions in order to adjust their shape, motility and physiology. The histidine-aspartate phosphorelay signal-transduction system (also known as the two-component system) is important in cellular adaptation to environmental changes in both prokaryotes and lower eukaryotes. In this system, protein histidine kinases function as sensors and signal transducers. The Escherichia coli osmosensor, EnvZ, is a transmembrane protein with histidine kinase activity in its cytoplasmic region. The cytoplasmic region contains two functional domains: domain A (residues 223-289) contains the conserved histidine residue (H243), a site of autophosphorylation as well as transphosphorylation to the conserved D55 residue of response regulator OmpR, whereas domain B (residues 290-450) encloses several highly conserved regions (G1, G2, F and N boxes) and is able to phosphorylate H243. Here we present the solution structure of domain B, the catalytic core of EnvZ. This core has a novel protein kinase structure, distinct from the serine/threonine/tyrosine kinase fold, with unanticipated similarities to both heatshock protein 90 and DNA gyrase B.
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PMID:NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ. 981 6

We identified in deepwater rice (Oryza sativa L.) a gene encoding a leucine-rich repeat receptor-like transmembrane protein kinase, OsTMK (O. sativa transmembrane kinase). The transcript levels of OsTMK increased in the rice internode in response to gibberellin. Expression of OsTMK was especially high in regions undergoing cell division and elongation. The kinase domain of OsTMK was enzymatically active, autophosphorylating on serine and threonine residues. A cDNA encoding a rice ortholog of a kinase-associated type 2C protein phosphatase (OsKAPP) was cloned. KAPPs are putative downstream components in kinase-mediated signal transduction pathways. The kinase interaction domain of OsKAPP was phosphorylated in vitro by the kinase domain of OsTMK. RNA gel-blot analysis indicated that the expression of OsTMK and OsKAPP was similar in different tissues of the rice plant. In protein-binding assays, OsKAPP interacted with a receptor-like protein kinase, RLK5 of Arabidopsis, but not with the protein kinase domains of the rice and maize receptor-like protein kinases Xa21 and ZmPK1, respectively.
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PMID:Expression of a gibberellin-induced leucine-rich repeat receptor-like protein kinase in deepwater rice and its interaction with kinase-associated protein phosphatase. 1036 8

Many, if not most, bacterial species swim. The synthesis and operation of the flagellum, the most complex organelle of a bacterium, takes a significant percentage of cellular energy, particularly in the nutrient limited environments in which many motile species are found. It is obvious that motility accords cells a survival advantage over non-motile mutants under normal, poorly mixed conditions and is an important determinant in the development of many associations between bacteria and other organisms, whether as pathogens or symbionts and in colonization of niches and the development of biofilms. This survival advantage is the result of sensory control of swimming behaviour. Although too small to sense a gradient along the length of the cell, and unable to swim great distances because of buffetting by Brownian motion and the curvature resulting from a rotating flagellum, bacteria can bias their random swimming direction towards a more favourable environment. The favourable environment will vary from species to species and there is now evidence that in many species this can change depending on the current physiological growth state of the cell. In general, bacteria sense changes in a range of nutrients and toxins, compounds altering electron transport, acceptors or donors into the electron transport chain, pH, temperature and even the magnetic field of the Earth. The sensory signals are balanced, and may be balanced with other sensory pathways such as quorum sensing, to identify the optimum current environment. The central sensory pathway in this process is common to most bacteria and most effectors. The environmental change is sensed by a sensory protein. In most species examined this is a transmembrane protein, sensing the external environment, but there is increasing evidence for additional cytoplasmic receptors in many species. All receptors, whether sensing sugars, amino acids or oxygen, share a cytoplasmic signalling domain that controls the activity of a histidine protein kinase, CheA, via a linker protein, CheW. A reduction in an attractant generally leads to the increased autophosphorylation of CheA. CheA passes its phosphate to a small, single domain response regulator, CheY. CheY-P can interact with the flagellar motor to cause it to change rotational direction or stop. Signal termination either via a protein, CheZ, which increases the dephosphorylation rate of CheY-P or via a second CheY which acts as a phosphate sink, allows the cell to swim off again, usually in a new direction. In addition to signal termination the receptor must be reset, and this occurs via methylation of the receptor to return it to a non-signalling conformation. The way in which bacteria use these systems to move to optimum environments and the interaction of the different sensory pathways to produce species-specific behavioural response will be the subject of this review.
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PMID:Bacterial tactic responses. 1050 Aug 47


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