R E V I E W S:

Benjamin M. Gaston, Jeannean Carver, Allan Doctor, and Lisa A. Palmer: S-Nitrosylation Signaling in Cell Biology
Mol. Interv. 2003 3: 253-263. [Summary] [Full Text] [PDF]
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.

Jonathan A. Hata and Walter J. Koch: Phosphorylation of G Protein–Coupled Receptors: GPCR Kinases in Heart Disease
Mol. Interv. 2003 3: 264-272. [Summary] [Full Text] [PDF]
{beta}-Adrenergic receptors ({beta}ARs), specific members of the G protein-coupled receptor (GPCR) superfamily, regulate cardiac output and activity in response to catecholamines. {beta}AR kinases ({beta}ARKs) modulate {beta}AR activity by directly phosphorylating the receptors and abrogating {beta}AR-dependent signals. Amounts of {beta}ARK1 are increased in cardiac disease, where cardiac output is below normal, suggesting that the impairment of {beta}AR 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 {beta}ARKs.

Michele R. Wing, David M. Bourdon, and T. Kendall Harden: PLC- ${varepsilon}$ : A Shared Effector Protein in Ras-, Rho-, and G ${alpha}$ ß ${gamma}$ -Mediated Signaling
Mol. Interv. 2003 3: 273-280. [Summary] [Full Text] [PDF]
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-{varepsilon}), appears to be regulated by Ras- and Rho-mediated signals as well as by G{alpha}12/13-dependent pathways. Thus, PLC-{varepsilon} 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.

Jason Matthews and Jan-Åke Gustafsson: Estrogen Signaling: A Subtle Balance Between ER ${alpha}$ and ERß
Mol. Interv. 2003 3: 281-292. [Summary] [Full Text] [PDF]
Estrogen-dependent effects upon cells and tissues are mediated by two receptors, ER{alpha} and the increasingly well-characterized ER{beta}. The activities of ER{alpha} and ER{beta} exhibit some cell-type- and promoter-context sensitivity. ER{beta} antagonizes the actions of ER{alpha} in several established in vitro and in vivo models, and ER{beta} appears to have less transcriptional activity on chromatin templates than does ER{alpha}. Whether ER{beta} only serves to hinder the activity of ER{alpha} 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.

D E P A R T M E N T S:

Erratum:

Douglas A. Bayliss, Jay E. Sirois, and Edmund M. Talley: erratum: The TASK Family: Two-Pore Domain Background K+ Channels
Mol. Interv. 2003 3: 252. [Full Text] [PDF]

CrossTalk:

Interviews with people in the world of pharmacology