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)

It is evident from the above review that during the last two decades a great deal of interest in investigating the action of serotonin in parasitic worms has been shown by parasitologists as well as by scientists from several other disciplines. What we have initially reported concerning the effect of serotonin on motility and carbohydrate metabolism of F. hepatica has been pursued on several other parasitic worms. The studies so far indicate that serotonin stimulates motility of every species tested among the phylum Platyhelminthes. The indoleamine also stimulates glycogenolysis in the few flatworm parasites that have been investigated. The information in nematodes is scanty and the role of serotonin in these parasites is still open for experimentation. Recent biochemical investigations on F. hepatica and S. mansoni demonstrated that serotonin and related compounds utilize a common class of receptors in plasma membrane particles which I designate as 'serotonin receptors'. These receptors are linked to an adenylate cyclase that catalyses the synthesis of the second messenger, cyclic 3',5'-AMP. Serotonin and its congeners increase the concentration of cyclic AMP in intact parasites whereas antagonists inhibit such an effect. Cyclic AMP stimulates glycogenolysis, glycolysis and some rate-limiting glycolytic enzymes. It activates a protein kinase that may be involved in activation of glycogen phosphorylase and phosphofructokinase. Serotonin-activated adenylate cyclase in S. mansoni is activated early in the life of the schistosomule. The possibility is discussed that the availability of cyclic AMP through serotonin activation in these parasites may be a prelude to the development processes that take place in the parasite. The different components of the serotonin-activated adenylate cyclase in the parasite are the same as those that have been previously described for the host. Binding characteristics of the receptors indicate that the receptors in F. hepatica appear to be different from those that have been described in the host. The discovery of these receptors and their differences from those in the host offer a new site which is amenable to pharmacological manipulation. The search for new agents that influence serotonin receptors in these parasites could be included in a strategy for the development of new chemotherapeutic agents against these parasites.
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PMID:Serotonin receptors in parasitic worms. 615 76

The investigation of protein kinase activity in different life stages of a few filarial worms indicates the presence of different protein kinases and of dissimilarities between the distribution pattern of these enzymes during the development. Phosvitin turned out to be the preferred exogenous acceptor protein, when homogenates of adults of Brugia malayi, Dipetalonema viteae, Setaria cervi and Litomosoides carinii were used as source of enzyme. In contrast to adults the L3-larval and the microfilarial stages demonstrated much lower phosvitin phosphorylating activity and the preference for acidic and basic proteins as phosphate acceptors was about equal. The occurrence of cyclic AMP-dependent protein kinase was established for adults of B. malayi.
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PMID:Protein kinases in different life stages of Brugia malayi and other filarial worms. 654 23

Human WEE1 (WEE1Hu) was cloned on the basis of its ability to rescue wee1+ mutants in fission yeast [Igarashi, M., Nagata, A., Jinno, S., Suto, K. & Okayama, H. (1991) Nature (London) 353, 80-83]. Biochemical studies carried out in vitro with recombinant protein demonstrated that WEE1Hu encodes a tyrosine kinase of approximately 49 kDa that phosphorylates p34cdc2 on Tyr-15 [Parker, L. L. & Piwnica-Worms, H. (1992) Science 257, 1955-1957]. To study the regulation of WEE1Hu in human cells, two polyclonal antibodies to bacterially produced p49WEE1Hu were generated. In addition, a peptide antibody generated against amino acids 361-388 of p49WEE1Hu was also used. Unexpectantly, these antibodies recognized a protein with an apparent molecular mass of 95 kDa in HeLa cells, rather than one of 49 kDa. Immunoprecipitates of p95 phosphorylated p34cdc2 on Tyr-15, indicating that p95 is functionally related to p49WEEIHu, and mapping studies demonstrated that p95 is structurally related to p49WEE1Hu. In addition, the substrate specificity of p95 was more similar to that of fission yeast p107wee1 than to that of human p49WEE1. Finally, the kinase activity of p95 toward p34cdc2/cyclin B was severely impaired during mitosis. Taken together, these results indicate that the original WEE1Hu clone isolated in genetic screens encodes only the catalytic domain of human WEE1 and that the authentic human WEE1 protein has an apparent molecular mass of approximately 95 kDa.
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PMID:Identification of a 95-kDa WEE1-like tyrosine kinase in HeLa cells. 756 88

Mutant alleles of the genes age-1 and daf-2 that lengthen life span (Age phenotype) of Caenorhabditis elegans cause higher protein kinase (PKA, PKC, PTK) activity levels in senescing worms relative to wild-type. Elevated levels of PKA and PTK were also present in dauer larvae, developmentally arrested juveniles specialized for long-term survival, relative to L3 larvae, the alternative developmental stage. PKC activity was downregulated in dauers of a non-Age control strain and in age-1 mutant dauers, compared to L3 larvae, but similar activities were measured in dauers and L3 larvae of a daf-2 mutant strain. Thus, age-1 and daf-2 mutant worms may express distinct elements of a dauer-specific survival program during adult life.
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PMID:Modulation of kinase activities in dauers and in long-lived mutants of Caenorhabditis elegans. 922 26

Withdrawal from the cell cycle as cells begin to differentiate is accomplished by the downregulation of cyclin-dependent kinase activities in G1 phase. Recent analysis of loss-of-function mutations in flies, worms, and mice has provided insight into the roles of various negative regulators of G1 phase in developing organisms.
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PMID:Controlling cell proliferation in differentiating tissues: genetic analysis of negative regulators of G1-->S-phase progression. 942 41

Successful mitosis requires faithful DNA replication, spindle assembly, chromosome segregation, and cell division. In the budding yeast Saccharomyces cerevisiae, the G(2)-to-M transition requires activation of Clb-bound forms of the protein kinase, Cdc28. These complexes are held in an inactive state via phosphorylation of Tyr19 in the ATP-binding loop of Cdc28 by the Swe1 protein kinase. The HSL1 and HSL7 gene products act as negative regulators of Swe1. Hsl1 is a large (1,518-residue) protein kinase with an N-terminal catalytic domain and a very long C-terminal extension. Hsl1 localizes to the incipient site of cytokinesis in the bud neck in a septin-dependent manner; however, the function of Hsl7 was not previously known. Using both indirect immunofluorescence with anti-Hsl7 antibodies and a fusion of Hsl7 to green fluorescent protein, we found that Hsl7 also localizes to the bud neck, congruent with the septin ring that faces the daughter cell. Both Swe1 and a segment of the C terminus of Hsl1 (which has no sequence counterpart in two Hsl1-related protein kinases, Gin4 and Kcc4) were identified as gene products that interact with Hsl7 in a two-hybrid screen of a random S. cerevisiae cDNA library. Hsl7 plus Swe1 and Hsl7 plus Hsl1 can be coimmunoprecipitated from extracts of cells overexpressing these proteins, confirming that Hsl7 physically associates with both partners. Also consistent with the two-hybrid results, Hsl7 coimmunoprecipitates with full-length Hsl1 less efficiently than with a C-terminal fragment of Hsl1. Moreover, Hsl7 does not localize to the bud neck in an hsl1Delta mutant, whereas Hsl1 is localized normally in an hsl7Delta mutant. Phosphorylation and ubiquitinylation of Swe1, preludes to its destruction, are severely reduced in cells lacking either Hsl1 or Hsl7 (or both), as judged by an electrophoretic mobility shift assay. Collectively, these data suggest that formation of the septin rings provides sites for docking Hsl1, exposing its C terminus and thereby permitting recruitment of Hsl7. Hsl7, in turn, presents its cargo of bound Swe1, allowing phosphorylation by Hsl1. Thus, Hsl1 and Hsl7 promote proper timing of cell cycle progression by coupling septin ring assembly to alleviation of Swe1-dependent inhibition of Cdc28. Furthermore, like septins and Hsl1, homologs of Hsl7 are found in fission yeast, flies, worms, and humans, suggesting that its function in this control mechanism may be conserved in all eukaryotes.
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PMID:Hsl7 localizes to a septin ring and serves as an adapter in a regulatory pathway that relieves tyrosine phosphorylation of Cdc28 protein kinase in Saccharomyces cerevisiae. 1049 Jun 48

The Wnt signalling cascade is essential for the development of both invertebrates and vertebrates, and is altered during tumorigenesis. Although a general framework for Wnt signalling has been elucidated, not all of the components have been identified. Here we describe a serine kinase, casein kinase I (CKI), which was isolated by expression cloning in Xenopus embryos. CKI reproduces several properties of Wnt signals, including generation of complete dorsal axes, stabilization of beta-catenin and induction of genes that are direct targets of Wnt signals. Dominant-negative forms of CKI and a pharmacological blocker of CKI inhibited Wnt signals in Xenopus. Inhibiting CKI in Caenorhabditis elegans generated worms with a mom phenotype, indicative of a loss of Wnt signals. In addition, CKI bound to and increased the phosphorylation of dishevelled, a known component of the Wnt pathway. These data indicate that CKI may be a conserved component of the Wnt pathway.
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PMID:Casein kinase I transduces Wnt signals. 1051 32

MAP kinases are a family of protein kinases that are ubiquitously expressed and play roles in most signal transduction pathways. They are activated within protein kinase cascades consisting of at least three kinases acting in series. In many, if not all cases, the three-kinase cascade, conveniently referred to as a MAP kinase module, is organized on scaffolds with a variety of forms and functions. This review discusses similarities and differences in scaffolding proteins and mechanisms in yeast, flies, worms and mammals.
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PMID:Scaffolding and protein interactions in MAP kinase modules. 1064 60

Previously we have shown that in the filarial parasite Brugia malayi, stimulation with murine epidermal growth factor (EGF) upregulated the expression of the nuclear GTPase, Ran. In this paper we provide further evidence that filarial parasites possess the ability to respond to mammalian EGF. Stimulation of B. malayi microfilariae with EGF increased transcription of a Raf kinase, increased the physical interaction between Ran and at least eight unidentified proteins, abolished the association of a putative EGF receptor with the nuclear GTPase Ran and enhanced phosphorylation of native microfilarial proteins. In the cattle filarial parasite Setaria digitata, stimulation of adult worms with EGF was probably responsible for up-regulation of a DP-1 family transcription factor. These data suggest that filarial parasites possess the ability to respond to mammalian EGF and that mammalian growth factors may regulate developmental maturation of filarial parasites.
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PMID:Upregulation of a raf kinase and a DP-1 family transcription factor in epidermal growth factor (EGF) stimulated filarial parasites. 1099 27

In the nemertean worms Cerebratulus lacteus and Micrura alaskensis, 5-HT (=5-hydroxytryptamine, or serotonin) causes prophase-arrested oocytes to mature and complete germinal vesicle breakdown (GVBD). To identify the intracellular pathway that mediates 5-HT stimulation, follicle-free oocytes of nemerteans were assessed for GVBD rates in the presence or absence of 5-HT after being treated with various modulators of cAMP, a well known transducer of 5-HT signaling and an important regulator of hormone-induced maturation in general. Unlike in many animals where high levels of intra-oocytic cAMP block maturation, treatment of follicle-free nemertean oocytes with agents that elevate cAMP (8-bromo-cAMP, forskolin or inhibitors of phosphodiesterases) triggered GVBD in the absence of added 5-HT. Similarly, 5-HT caused a substantial cAMP increase prior to GVBD in nemertean oocytes that had been pre-injected with a cAMP fluorosensor. Such a rise in cAMP seemed to involve G-protein-mediated signaling and protein kinase A (PKA) stimulation, based on the inhibition of 5-HT-induced GVBD by specific antagonists of these transduction steps. Although the downstream targets of activated PKA remain unknown, neither the synthesis of new proteins nor the activation of MAPKs (mitogen-activated protein kinases) appeared to be required for GVBD after 5-HT stimulation. Alternatively, pre-incubation in roscovitine, an inhibitor of maturation-promoting factor (MPF), prevented GVBD, indicating that maturing oocytes eventually need to elevate their MPF levels, as has been documented for other animals. Collectively, this study demonstrates for the first time that 5-HT can cause immature oocytes to undergo an increase in cAMP that stimulates, rather than inhibits, meiotic maturation. The possible relationship between such a form of oocyte maturation and that observed in other animals is discussed.
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PMID:5-HT causes an increase in cAMP that stimulates, rather than inhibits, oocyte maturation in marine nemertean worms. 1126 41


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