Table of Contents

July 2002; 2 (4)

Speaking of Pharmacology

    • Martin C. Michel,
    • Jeffrey R. Jasper,
    • and Paul Insel

    Adrenoceptors: A Convergence of Thinking

    Mol Interv July 2002 2:198-200; doi:10.1124/mi.2.4.198

Reflections

    • Susan L. Speaker

    Creating a Monster: Newspapers, Magazines, and America’s Drug Problem

    Mol Interv July 2002 2:201-204; doi:10.1124/mi.2.4.201

Viewpoints

    • Shunsuke Chikuma and
    • Jeffrey A. Bluestone

    CTLA-4: Acting at the Synapse

    Mol Interv July 2002 2:205-208; doi:10.1124/mi.2.4.205

    Egen and Allison have reported that cytotoxic T lymphocyte antigen-4 (CTLA-4), an immune-response–inhibiting protein, accumulates in a two-step process at immune synapses (the sites of physical contact between T cells and antigen-presenting cells). Depending upon the strength of the signal through the T cell receptor (TCR), CTLA-4 may reside at a cytoplasmic location near the synapse (in instances of weaker stimulation) or localize to the synapse itself (under strong TCR signaling conditions). Chikuma and Bluestone discuss these findings and how CTLA-4 might inhibit T cell activation, either by increasing the threshold for activation, or by dampening existing immune responses. These findings also have important ramifications for autoimmunity and the breadth of T cell proliferation (diverse vs. narrow clonal expansion) in immune responses.

    • Lee M. Graves,
    • Jun Han,
    • and H. Shelton Earp III

    Transactivation of the EGF Receptor: Is the PDGF Receptor an Unexpected Accomplice?

    Mol Interv July 2002 2:208-212; doi:10.1124/mi.2.4.208

    Saito et al. have observed that the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR) can heterodimerize at the plasma membrane and transduce signals that are measured by changes in ERK activation. Are these signaling outputs physiologically relevant? Graves, Han, and Earp discuss the observations made by Saito et al., and put forth possible mechanistic models of crosstalk between the EGFR and PDGFR. Such heterodimerization, if tightly regulated, likely has a role in normal cell physiology. There are also implications for carcinogenesis.

    • Claudia Wietek and
    • Luke A. O’Neill

    IRAK-4: A New Drug Target in Inflammation, Sepsis, and Autoimmunity

    Mol Interv July 2002 2:212-215; doi:10.1124/mi.2.4.212

    Two very recent publications, by Suzuki et al. and Li et al., describe the cloning, characterization, and the effects of knockout mice deficient in interleukin-1-associated receptor kinase-4 (IRAK-4), the newest member of the IRAK family. IRAK-4 requires its kinase activity to activate NF-κB, and IRAK-4 also activates MAP kinases. Wietek and O’Neill discuss the data indicating that IRAK-4 lies upstream of and activates IRAK-1, and that IRAK-4 is essential for innate immunity.

    • Sharen E. McKay and
    • Leonard K. Kaczmarek

    Act Locally: New Ways of Regulating Voltage-Gated Ion Channels

    Mol Interv July 2002 2:215-218; doi:10.1124/mi.2.4.215

    A very recent publication by Aydar et al. describes how sigma receptors, which can bind psychoactive compounds and might regulate responses to stress, can interact with potassium receptors, and how (in the presence or absence of ligand) sigma receptors can differentially affect these potassium channels. MacKay and Kaczmarek discuss results that suggest a new mechanism of channel regulation and have implications for potassium channel research (including the possible development of clinical targets).

Reviews

    • Karen J. Ho and
    • James K. Liao

    Non-nuclear Actions of Estrogen: New Targets for Prevention and Treatment of Cardiovascular Disease

    Mol Interv July 2002 2:219-228; doi:10.1124/mi.2.4.219

    Textbook accounts of estrogen lead one to envision estrogen receptors (ERs) shedding their inhibitory protein partners, dimerizing, and translocating to the nucleus. More recent observations indicate that ERs lead another lifestyle as well: as immediate participants in signal transduction. Non-nuclear or non-genomic effects of ER action include the protection of cardiac muscle and vascular smooth muscle cells, but much more remains to be discovered.

    • Anthony O. Fedele,
    • Murray L. Whitelaw,
    • and Daniel J. Peet

    Regulation of Gene Expression by the Hypoxia-Inducible Factors

    Mol Interv July 2002 2:229-243; doi:10.1124/mi.2.4.229

    When the delivery of oxygen to tissues or individual cells becomes less than adequate—a state termed hypoxia—the expression of many hypoxia-sensitive genes is stimulated by the transcription factors Hypoxia-Inducible Factor-1α (HIF-1α) and HIF-2α. Normally labile, the HIF-α proteins undergo hydroxylation on key residues that effectively promotes their degradation and increases specific gene expression. HIF-α proteins and their effectors are not only involved in normal processes such as erythropoiesis and angiogenesis, but are also activated in aberrant states including cancer. Thus, understanding the mechanisms by which HIF-1α and HIF-2α are regulated may lead to useful clinical therapeutic drugs.

    • Brian K. Kwon,
    • Jaimie F. Borisoff,
    • and Wolfram Tetzlaff

    Molecular Targets for Therapeutic Intervention after Spinal Cord Injury

    Mol Interv July 2002 2:244-258; doi:10.1124/mi.2.4.244

    Thousands of active people are rendered immobile each year in North America alone by spinal cord injury. In the face of this health concern, much recent research has illuminated the multiple processes whereby endogenous factors in the grievously injured spinal cord prevent axonal growth and regeneration. With the identification of the molecular networks that participate in inhibiting axon regeneration, the future is looking brighter for therapeutic interventions that will help the paralyzed walk again.

Beyond the Bench

Outliers

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This Issue

July 2002; 2 (4)
Cover
  1. Speaking of Pharmacology
  2. Reflections
  3. Viewpoints
  4. Reviews
  5. Beyond the Bench
  6. Outliers

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