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)

In airway smooth muscle cells ligand binding to the seven-transmembrane endothelin and thrombin receptors stimulates cell growth. Rapid activation of the extracellular regulated kinase 2 and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases was also observed. The results demonstrate a novel mechanism of seven-transmembrane receptor signaling involving activation of the Jun kinase pathway. Receptor coupling to Jun kinase activation may involve heterotrimeric G proteins since the kinase was enzymatically activated in cells treated with aluminum fluoride. The activity of Raf-1, measured by immune complex kinase assay, revealed that platelet-derived growth factor and phorbol 12-myristate 13-acetate both stimulated Raf-1 activity, while thrombin and endothelin did not appreciably stimulate Raf-1. The data suggest that endothelin and thrombin stimulate Raf-1-independent mechanisms of mitogen-activated protein kinase activation. Endothelin- or thrombin-induced activation of mitogen-activated protein kinases was significantly inhibited by activation of cyclic AMP-dependent protein kinase by forskolin. Proliferation of airway smooth muscle cells, measured by incorporation of [3H]thymidine into DNA, was also greatly attenuated by forskolin.
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PMID:The seven-transmembrane-spanning receptors for endothelin and thrombin cause proliferation of airway smooth muscle cells and activation of the extracellular regulated kinase and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases. 862 41

The regulation of synaptic signal transduction is of central importance to our understanding of normal and abnormal nervous system function. One mechanism by which signal transduction can be affected is the modification of cellular sensitivity by alterations of transmembrane receptor properties. For G-protein coupled receptors, protein phosphorylation is intimately involved in many stages of receptor regulation. This appears to be true for ionotropic receptors as well. Evidence of a role for protein kinase and protein phosphatase activity in the multi-staged ionotropic receptor regulation cascade is presented and a comparison to G-protein coupled receptor regulation is considered.
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PMID:Regulation of ionotropic receptors by protein phosphorylation. 863 82

ARK1 is a vegetatively expressed receptor protein kinase gene isolated from Arabidopsis thaliana based on its sequence similarity to Brassica genes involved in pollen-stigma signaling and the self-incompatibility response. This paper shows that the kinase domain of ARK1 autophosphorylates on serine and threonine residues when expressed as a recombinant fusion protein. ARK1 produces a 2.9 kb transcript encoding a transmembrane receptor protein kinase and a 1.4 kb transcript encoding the receptor domain alone. Constitutive high-level expression of ARK1 transcripts in transgenic Arabidopsis resulted in severe stunting and also disrupted normal cellular expansion and differentiation.
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PMID:An S-locus-related gene in Arabidopsis encodes a functional kinase and produces two classes of transcripts. 881 66

A complex signal transduction pathway functions in the early Drosophila embryo to establish dorsal-ventral polarity. Activation of this pathway results in the nuclear transport of the protein dorsal (dl), a member of the rel/NF-kappaB family of transcription factors. Genetic studies have identified three intracellular components whose activity is required for activation of dl: Toll, a transmembrane receptor; pelle (pll), a serine/threonine protein kinase; and tube, a protein of unknown function. Here we examine the activities of these proteins when coexpressed in Drosophila Schneider cells. Coexpression of pll with dl enhanced dl nuclear localization and resulted in a modest increase in transcriptional activity. However, when pll was coexpressed with a specific mutant derivative of Toll (TlNaeI), although not with wild-type Toll, a striking synergistic activation of dl was detected. Unexpectedly, coexpression of pll plus TlNaeI, in the absence of dl, resulted in a similar synergistic activation of a GAL4-tube fusion protein. Based on these and other results, we propose a model in which pll receives a signal from activated Toll and phosphorylates tube, which then participates directly in dl activation.
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PMID:Functional interactions between the pelle kinase, Toll receptor, and tube suggest a mechanism for activation of dorsal. 884 22

The histidyl-aspartyl phosphorelay, formerly described as the two-component system, is the predominant mode of signal transduction in bacteria. Adaptation to environmental changes occurs through a sensor histidine protein kinase and a response regulator. The histidine protein kinase is usually a transmembrane receptor and the response regulator is a cytoplasmic protein. Together the histidyl-aspartyl phosphorelay proteins mediate reversible phosphorylation events that control downstream effectors. Following autophosphorylation at a conserved histidine residue, the histidine kinase serves as a phospho-donor for the response regulator. Once phosphorylated, the response regulator mediates changes in gene expression or cellular locomotion. The EnvZ-OmpR phosphorelay system in Escherichia coli, which monitors external osmolarity and responds by differentially modulating the expression of the OmpF and OmpC major outer membrane porins, will be described as a model system. While histidine kinases were thought to be present only in prokaryotes, they have recently been identified in eukaryotic systems. Here, we review the unique and conserved features of this growing family of signal transducers.
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PMID:Signal transduction via the histidyl-aspartyl phosphorelay. 918 55

A signaling pathway active on the ventral side of the Drosophila embryo defines dorsoventral polarity. A cell surface signal relayed by Toll, Tube and Pelle releases the Rel-related protein Dorsal from its cytoplasmic inhibitor Cactus; free Dorsal translocates into nuclei and directs expression of ventral fates. Using the yeast two-hybrid system and immunoprecipitation experiments, we define scaffolding and anchoring interactions among the pathway components. We show that Dorsal binds specifically to Tube, Pelle and Cactus, and that the protein kinase activity of Pelle differentially regulates its interactions with Dorsal and Tube. We also identify Drosophila Filamin as a potential adaptor linking the interaction network, via Tube, to the transmembrane receptor Toll.
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PMID:An activity-dependent network of interactions links the Rel protein Dorsal with its cytoplasmic regulators. 936 41

Determination of dorsal/ventral polarity in Drosophila requires 12 genetically defined, maternally encoded proteins. These include Toll, a transmembrane receptor, Pelle, a ser/thr protein kinase and Tube, all of which function intracytoplasmically to initiate the cascade that ultimately activates Dorsal, an NF-kappaB family transcription factor. Here we describe biochemical interactions between recombinant Toll, Pelle and Tube that provide insights into early events in activation of the signaling cascade. We first show that Pelle binds directly to a region within the Toll intracytoplasmic domain, providing the first evidence that these two evolutionarily conserved molecules physically interact. We then demonstrate that Pelle can be autophosphorylated, and that this prevents binding to Toll as well as Tube. Autophosphorylation occurs in the N-terminal, death-domain-containing region of Pelle, which is dispensable for binding to Toll but required for enzymatic activity. We also show that Pelle phosphorylates Toll, within the region required for Pelle interaction, but this phosphorylation can be blocked by a previously characterized inhibitory domain at the Toll C terminus. These and other results allow us to propose a model by which multiple phosphorylation-regulated interactions between these three proteins lead to activation of the Dorsal signaling pathway.
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PMID:Phosphorylation modulates direct interactions between the Toll receptor, Pelle kinase and Tube. 980 20

Recent evidence (1) suggests that the related peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) bind to the same heptahelical transmembrane receptor, with receptor specificity being determined by a receptor associated modifying protein (RAMP). If correct, this hypothesis would predict that each peptide should desensitize the cellular response to subsequent stimulation by itself or the other peptide. We have therefore studied the patterns of desensitization of these receptors in SK-N-MC cells. SK-N-MC cells were stimulated for 20 minutes in either serum free medium alone (control) or SFM containing AM 10(-8) M or CGRP 10(-7) M. Cells were then incubated for a further 20 minutes in SFM containing a second agonist and 1 mM isobutyryl methylxanthine (IBMX), before harvesting and assay for cAMP. Pre-exposure of cells to CGRP or AM decreased cAMP generation in response to subsequent stimulation with CGRP by 58% (+/-14) and 42% (+/-14) (SD) respectively. Pre-incubation of cells with 100 nM H-89 abolished this effect, indicating that desensitization was mediated through PKA. In contrast, there was no attenuation of the cAMP response to stimulation with AM by pre-exposure to AM or CGRP. These results suggest that CGRP and AM receptors exhibit different patterns of desensitization in SK-N-MC cells: a finding with significant implications for the RAMP hypothesis.
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PMID:Desensitization of CGRP and adrenomedullin receptors in SK-N-MC cells: implications for the RAMP hypothesis. 988 66

Hypothalamic growth hormone-releasing hormone (GHRH) stimulates growth hormone (GH) gene expression in anterior pituitary somatotrophs by binding to the GHRH receptor, a G-protein-coupled transmembrane receptor, and by mediating a cAMP-mediated protein kinase A (PKA) signal-transduction pathway. Two nonclassical cAMP-response element motifs (CGTCA) are located at nucleotides -187/-183 (distal cAMP-response element; dCRE) and -99/-95 (proximal cAMP-response element; pCRE) of the human GH promoter and are required for cAMP responsiveness, along with the pituitary-specific transcription factor Pit-1 (official nomenclature, POU1F1). Although a role for cAMP-response element binding protein (CREB) in GH stimulation by PKA has been suggested, it is unclear how the effect may be mediated. CREB binding protein (CBP) is a nuclear cofactor named for its ability to bind CREB. However, CBP also binds other nuclear proteins. We determined that CBP interacts with Pit-1 and is a cofactor for Pit-1-dependent activation of the human GH promoter. This pathway appears to be independent of CREB, with CPB being the likely target of phosphorylation by PKA.
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PMID:CREB-independent regulation by CBP is a novel mechanism of human growth hormone gene expression. 1052 51

In the S locus-controlled self-incompatibility system of Brassica, recognition of self-related pollen at the surface of stigma epidermal cells leads to inhibition of pollen tube development. The female (stigmatic) determinant of this recognition reaction is a polymorphic transmembrane receptor protein kinase encoded at the S locus. Another highly polymorphic, anther-expressed gene, SCR, also encoded at the S locus, fulfills the requirements for the hypothesized pollen determinant. Loss-of-function and gain-of-function studies prove that the SCR gene product is necessary and sufficient for determining pollen self-incompatibility specificity, possibly by acting as a ligand for the stigmatic receptor.
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PMID:The male determinant of self-incompatibility in Brassica. 1061 May 66


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