Table of Contents

Reviews

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  • Benjamin M. Gaston,
  • Jeannean Carver,
  • Allan Doctor,
  • and Lisa A. Palmer

  S-Nitrosylation Signaling in Cell Biology

  Mol Interv August 2003 3:253-263; doi:10.1124/mi.3.5.253
  • Abstract
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  A plethora of proteins are modified by many different posttranslational covalent changes, most notably phosphorylation and glycosylation. However, the nitrosylation of protein cysteine residues (S-nitrosylation) by nitric oxide is an increasingly appreciated modification whose biological effects (such as changes in enzymatic activity) are now becoming more widely studied. S-Nitrosylation is a highly controlled process and, indeed, intracellular substrates have been identified that act to store S-nitrothiols (SNOs) until these SNOs are needed for rapid response to upstream signals. Unbalanced regulation of SNO concentrations in cells may also lead to or exacerbate disease states. It is, therefore, critical to understand the underlying processes that mediate S-nitrosylation and denitrosylation for a better understanding of how to treat pathophysiological states associated with improper SNO regulation.

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  • Jonathan A. Hata and
  • Walter J. Koch

  Phosphorylation of G Protein–Coupled Receptors: GPCR Kinases in Heart Disease

  Mol Interv August 2003 3:264-272; doi:10.1124/mi.3.5.264
  • Abstract
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  β-Adrenergic receptors (βARs), specific members of the G protein-coupled receptor (GPCR) superfamily, regulate cardiac output and activity in response to catecholamines. βAR kinases (βARKs) modulate βAR activity by directly phosphorylating the receptors and abrogating βAR-dependent signals. Amounts of βARK1 are increased in cardiac disease, where cardiac output is below normal, suggesting that the impairment of βAR activity could lead to certain forms of heart disease. Thus, there is great interest in generating therapeutic agents that can modulate the activity of the βARKs.

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  • Michele R. Wing,
  • David M. Bourdon,
  • and T. Kendall Harden

  PLC-ε: A Shared Effector Protein in Ras-, Rho-, and Gαβγ-Mediated Signaling

  Mol Interv August 2003 3:273-280; doi:10.1124/mi.3.5.273
  • Abstract
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  The experimental integration of signaling pathways has resulted in a renewed appreciation for the finetuning and gradation of signaling endpoints that the cell uses to negotiate environmental queues and elaborate appropriate physiological responses. A recently identified isoform of phospholipase C, PLC-epsilon (PLC-ε), appears to be regulated by Ras- and Rho-mediated signals as well as by Gα_12/13-dependent pathways. Thus, PLC-ε functions as a node for convergent pathways that emanate from G protein-coupled receptors as well as from receptor tyrosine kinases, the former of which depend on heterotrimeric G proteins and the latter of which are regulated by the small monomeric GTPases Ras and Rho.

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  • Jason Matthews and
  • Jan-Åke Gustafsson

  Estrogen Signaling: A Subtle Balance Between ERα and ERβ

  Mol Interv August 2003 3:281-292; doi:10.1124/mi.3.5.281
  • Abstract
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  Estrogen-dependent effects upon cells and tissues are mediated by two receptors, ERα and the increasingly well-characterized ERβ. The activities of ERα and ERβ exhibit some cell-type- and promoter-context sensitivity. ERβ antagonizes the actions of ERα in several established in vitro and in vivo models, and ERβ appears to have less transcriptional activity on chromatin templates than does ERα. Whether ERβ only serves to hinder the activity of ERα is the subject of some debate, and the demonstrated presence of other existing isoforms of ERs further complicates the picture. Elucidating the biological functions of each receptor and their molecular regulation will provide researchers with a better understanding of estrogenic actions in normal and disease states.