Table of Contents

September 2003; 3 (6)


  • Several distinct mitogen-activated protein kinase (MAPK) pathways have been identified, including the extracellular signal-regulated kinase 1 and 2 (ERK 1-2), p38, ERK5, and c-Jun N-terminal kinase (JNK) cascades. Given that crosstalk exists between intracellular signaling “pathways,” it seems obvious that some level of regulation must exist to prevent competing (or parallel) signals from sending conflicting (or amplified) signals to downstream effectors. New evidence suggests that the JNK pathway inhibits signaling by the ERK pathway by uncoupling ERK from its upstream activator MEK (MAPK/ERK kinase), thereby promoting JNK-mediated signals to the transcriptional activator c-Jun. Does the JNK pathway function to inhibit ERK signals in general, or is this a cell type-specific phenomenon?


  • Within the last few years, a slew of engineered antibodies have entered into clinical trials for the treatment of a wide variety of diseases, from cancer to psoriasis. FDA-approved monoclonal antibody-based drugs for the treatment of rheumatoid arthritis exemplify the approaches to the engineering of antibodies that are being pursued by an ever-growing number of drug companies.

  • Understanding the association between propensity for disease and the specific array of receptor subtypes roduced in any individual remains an important goal within the context of many different hormone, neurotransmitter, and signal transduction studies. A focus on the two serotonin receptor subtypes 5-HT2A and 5-HT2C reveals the richness of biological mechanisms that can give rise to receptor diversity, regulate receptor subtype diversity over time, and contribute to the individual’s responses to signals in health and disease.

  • Humans have evolved a variety of enzymes, including the cytochromes P450, to protect themselves against chemical challenges from the environment. These enzyme systems frequently represent a barrier to the in vivo efficacy of administered drugs, and researchers who wish to develop a new drug must therefore be able to anticipate how the human drug-metabolizing machinery may act to thwart their best efforts. Because animal models do not always reflect drug metabolism as it occurs in humans, mice engineered through transgenic technologies to more accurately reflect human metabolism are becoming essential to modern experimental therapeutics.

Beyond the Bench

Net Results