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:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to elucidate aspects of the regulatory mechanisms leading to enhanced glucose metabolism and insulin sensitivity of muscle after physical exertion. Biopsies were obtained from the vastus lateralis muscle of healthy volunteers before and after 60 min of bicycle exercise at 60% of their maximal aerobic capacity. Insulin binding to wheat germ agglutinin-purified muscle insulin receptors as well as basal and insulin-stimulated receptor kinase activity toward an exogenous substrate were unaltered by exercise. Muscle glycogen levels diminished from 3.35 +/- 0.26 to 1.85 +/- 0.13 mg/100 mg muscle (P less than 0.01) and the half-maximal activation constant of glycogen synthase for glucose 6-phosphate decreased from 0.62 +/- 0.05 to 0.25 +/- 0.02 mM (P less than 0.001). Total glycogen synthase activity was unchanged. In the absence of phosphatase inhibitors, glucose 6-phosphate-independent glycogen synthase activity of the crude enzyme extract increased during in vitro incubation. The initial rate of activation (through dephosphorylations) of glycogen synthase was 0.18 +/- 0.06 vs. 0.37 +/- 0.03 U.min-1.mg-1 protein before and after exercise, respectively (P less than 0.02). The total as well as the glycogen-associated phosphoprotein phosphatase activity was, however, unaffected by exercise.
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PMID:Exercise-enhanced activation of glycogen synthase in human skeletal muscle. 216 1

Continuous growth and development in plants are accomplished by meristems, groups of undifferentiated cells that persist as stem cells and initiate organs. While the structures of the apical and floral meristems in dicotyledonous plants have been well described, little is known about the underlying molecular mechanisms controlling cell proliferation and differentiation in these structures. We have shown previously that the CLAVATA1 (CLV1) gene in Arabidopsis encodes a receptor kinase-like protein that controls the size of the apical and floral meristems. Here, we show that KAPP, a gene encoding a kinase-associated protein phosphatase, is expressed in apical and young floral meristems, along with CLV1. Overexpression of KAPP mimics the clv1 mutant phenotype. Furthermore, CLV1 has kinase activity: it phosphorylates both itself and KAPP. Finally, KAPP binds and dephosphorylates CLV1. We present a model where KAPP functions as a negative regulator of the CLAVATA1 signal transduction pathway.
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PMID:A possible role for kinase-associated protein phosphatase in the Arabidopsis CLAVATA1 signaling pathway. 929 34

Screening of a yeast two-hybrid library for proteins that interact with the kinase domain of an S-locus receptor kinase (SRK) resulted in the isolation of a plant protein called ARC1 (Arm Repeat Containing). This interaction was mediated by the C-terminal region of ARC1 in which five arm repeat units were identified. Using the yeast two-hybrid system and in vitro binding assays, ARC1 was found to interact specifically with the kinase domains from SRK-910 and SRK-A14 but failed to interact with kinase domains from two different Arabidopsis receptor-like kinases. In addition, treatment with a protein phosphatase or the use of a kinase-inactive mutant reduced or abolished the binding of ARC1 to the SRK-910 kinase domain, indicating that the interaction was phosphorylation dependent. Lastly, RNA blot analysis revealed that the expression of ARC1 is restricted to the stigma, the site of the self-incompatibility response.
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PMID:Binding of an arm repeat protein to the kinase domain of the S-locus receptor kinase. 941 84

The CLAVATA1 (CLV1) gene encodes a putative receptor kinase required for the proper balance between cell proliferation and differentiation in Arabidopsis shoot and flower meristems. Impaired CLV1 signaling results in masses of undifferentiated cells at the shoot and floral meristems. Although many putative receptor kinases have been identified in plants, the mechanism of signal transduction mediated by plant receptor-like kinases is largely unknown. One potential effector of receptor kinase signaling is kinase-associated protein phosphatase (KAPP), a protein that binds to multiple plant receptor-like kinases in a phosphorylation-dependent manner. To examine a possible role for KAPP in CLV1-dependent plant development, the interaction of CLV1 and KAPP was investigated in vitro and in vivo. KAPP binds directly to autophosphorylated CLV1 in vitro and co-immunoprecipitates with CLV1 in plant extracts derived from meristematic tissue. Reduction of KAPP transcript accumulation in an intermediate clv1 mutant suppresses the mutant phenotype, and the degree of suppression is inversely correlated with KAPP mRNA levels. These data suggest that KAPP functions as a negative regulator of CLV1 signaling in plant development. This may represent a general model for the interaction of KAPP with receptor kinases.
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PMID:Control of meristem development by CLAVATA1 receptor kinase and kinase-associated protein phosphatase interactions 970 78

The Arabidopsis wall-associated receptor kinase, Wak1, is a member of the Wak family (Wak1-5) that links the plasma membrane to the extracellular matrix. By the yeast two-hybrid screen, we found that a glycine-rich extracellular protein, AtGRP-3, binds to the extracellular domain of Wak1. Further in vitro binding studies indicated that AtGRP-3 is the only isoform among the six tested AtGRPs that specifically interacts with Waks, and the cysteine-rich carboxyl terminus of AtGRP-3 is essential for its binding to Wak1. We also show that Wak1 and AtGRP-3 form a complex with a molecular size of approximately 500 kDa in vivo in conjunction with the kinase-associated protein phosphatase, KAPP, that has been shown to interact with a number of plant receptor-like kinases. Binding of AtGRP-3 to Wak1 is shown to be crucial for the integrity of the complex. Wak1 and AtGRP-3 are both induced by salicylic acid treatment. Moreover, exogenously added AtGRP-3 up-regulates the expression of Wak1, AtGRP-3, and PR-1 (for pathogenesis-related) in protoplasts. Taken together, our data suggest that AtGRP-3 regulates Wak1 function through binding to the cell wall domain of Wak1 and that the interaction of Wak1 with AtGRP-3 occurs in a pathogenesis-related process in planta.
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PMID:Interaction of the Arabidopsis receptor protein kinase Wak1 with a glycine-rich protein, AtGRP-3. 1133 17

In signaling involving the transforming growth factor-beta (TGF-beta) superfamily of proteins, ligand binding brings the constitutively active type II receptor kinase into close proximity to its substrate, the type I receptor kinase, which it then activates by phosphorylation. The type I receptor kinase in turn phosphorylates one of the Smad family of transcription factors, which translocates to the nucleus and regulates gene expression. Smads are recruited to the receptor complex by an anchor protein, SARA (Smad anchor for receptor activation). Although several protein kinases in this pathway were known, including the receptors themselves, the relevant phosphatases had not previously been identified. Here we report the isolation of a Drosophila melanogaster homolog of SARA (Sara) in a screen for proteins that bind the catalytic subunit of type 1 serine/threonine protein phosphatase (PP1c). We identified a PP1c-binding motif in Sara, disruption of which reduced the ability of Sara to bind PP1c. Expression of this non-PP1c-binding mutant resulted in hyperphosphorylation of the type I receptor and stimulated expression of a target of TGF-beta signaling. Reducing PP1c activity enhanced the increase in the basal level of expression of genes responsive to Dpp (Decapentaplegic) caused by ectopic expression of the type II receptor Punt. Together these data suggest that PP1c is targeted to Dpp receptor complexes by Sara, where it acts as a negative regulator of Dpp signaling by affecting the phosphorylation state of the type I receptor.
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PMID:PP1 binds Sara and negatively regulates Dpp signaling in Drosophila melanogaster. 1213 49

The Arabidopsis genome sequence has revealed that plants contain a much larger complement of receptor kinase genes than other organisms. Early analysis of these genes revealed involvement in a diverse array of developmental and defense functions that included gametophyte development, pollen-pistil interactions, shoot apical meristem equilibrium, hormone perception, and cell morphogenesis. Amino acid sequence motifs and binding studies indicate that the ectodomains are capable of binding, either directly or indirectly, various classes of molecules including proteins, carbohydrates, and steroids. Genetic and biochemical approaches have begun to identify other components of several signal transduction pathways. Some receptor-like kinases (RLKs) appear to function with coreceptors lacking kinase domains, and genome analysis suggests this might be true for many RLKs. The KAPP protein phosphatase functions as a negative regulator of at least two RLK systems, and in vitro studies suggest it could be a common component of more. Whether plant signaling systems display a modularity similar to animal systems remains to be determined. Future efforts will reveal unknown functions of other RLKs and elucidate the relationships among their signaling networks.
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PMID:Receptor kinase signaling in plant development. 1214 67

This report describes a novel receptor-like kinase gene of tobacco (Nicotiana tabacum L.) that, in cell culture, is rapidly regulated by very low concentrations of cytokinin. The steady-state transcript level of the CYTOKONIN-REGULATED KINASE 1 gene (CRK1) was strongly reduced 30 min after cytokinin treatment. At higher concentrations abscisic acid and auxin induced a similar response. None of the other plant hormones tested elicited this response. Further analyses of the cytokinin-dependentregulation showed that the reduction of transcript was transient, and the duration of the recovery phase was dependent on the hormone concentration. CRKI is not a primary response gene as the simultaneous addition of cycloheximide inhibits its regulation by cytokinin. Inhibitor studies revealed that a protein phosphatase is likely involved in signalling processes upstream of CRK1. CRKI is expressed at low levels in the leaves, stem and roots of tobacco. It is predicted that the CRK1 protein is located in the plasma membrane. It has in its N-terminal putative receptor sequence a signal peptide, a serine- and a proline-rich region, a six repeat motif similar to the CRINKLY4 protein of Zea mays and several regions homologous to purine-binding motifs. A single transmembrane domain is followed by a highly conserved intracellular Ser/Thr kinase domain. Therefore, CRKI is a novel type of class I plant receptor kinase. We hypothesize that CRKI is involved in an early step of hormone signalling and that transcript down-regulation reflects a desensitization step in reaction to the signalling molecule.
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PMID:The CRK1 receptor-like kinase gene of tobacco is negatively regulated by cytokinin. 1217 9

Recognition of self-pollen during the self-incompatibility response in Brassica oleracea is mediated by the binding of a secreted peptide (the S locus cysteine-rich protein) to the S locus receptor kinase (SRK), a member of the plant receptor kinase (PRK) superfamily. Here, we describe the characterization of three proteins that interact with the cytosolic kinase domain of SRK. A B. oleracea homolog of Arabidopsis kinase-associated protein phosphatase was shown to interact with and dephosphorylate SRK and was itself phosphorylated by SRK. Yeast (Saccharomyces cerevisiae) two-hybrid screens identified two additional interactors, calmodulin and a sorting nexin, both of which have been implicated in receptor kinase down-regulation in animals. A calmodulin-binding site was identified in sub-domain VIa of the SRK kinase domain. The binding site is conserved and functional in several other members of the PRK family. The sorting nexin also interacted with diverse members of the PRK family, suggesting that all three of the interacting proteins described here may play a general role in signal transduction by this family of proteins.
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PMID:Interaction of calmodulin, a sorting nexin and kinase-associated protein phosphatase with the Brassica oleracea S locus receptor kinase. 1455 83

The cascade of phosphorylation is a pivotal event in transforming growth factor beta (TGFbeta) signaling. Reversible phosphorylation regulates fundamental aspects of cell activity. TGFbeta-induced Smad7 binds to type I receptor (TGFbeta type I receptor; TbetaRI) functioning as a receptor kinase antagonist. We found Smad7 interacts with growth arrest and DNA damage protein, GADD34, a regulatory subunit of the protein phosphatase 1 (PP1) holoenzyme, which subsequently recruits catalytic subunit of PP1 (PP1c) to dephosphorylate TbetaRI. Blocking Smad7 expression by RNA interference inhibits association of GADD34-PP1c complex with TbetaRI, indicating Smad7 acts as an adaptor protein in the formation of the PP1 holoenzyme that targets TbetaRI for dephosphorylation. SARA (Smad anchor for receptor activation) enhances the recruitment PP1c to the Smad7-GADD34 complex by controlling the specific subcellular localization of PP1c. Importantly, GADD34-PP1c recruited by Smad7 inhibits TGFbeta-induced cell cycle arrest and mediates TGFbeta resistance in responding to UV light irradiation. The dephosphorylation of TbetaRI mediated by Smad7 is an effective mechanism for governing negative feedback in TGFbeta signaling.
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PMID:GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. 1471 19


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