Current Signal Transduction Therapy - Volume 4, Issue 2, 2009

Cells respond to extracellular cues through a variety of receptors on the surface. These signals once transduced across the cell membrane, activate protein tyrosine kinases, which through phosphorylation of substrates on key tyrosine residues, are able to control cellular growth, activation and differentiation pathways. Recent data suggest that protein tyrosine kinases are critical in integrating signals from various Read More

The serotonin (5-HT) transporter (SERT) is implicated in numerous neuropsychiatric disorders including major depression and represents the main target for antidepressants, especially for the selective serotonin reuptake inhibitors (SSRIs). A recently developed SSRI has the particularity to enhance its own reuptake inhibitory activity via the allosteric modulation of SERT. In this review, the SSRI escitalopram, the (S)-enantiom Read More

High dose oestrogen therapy was used as a treatment for postmenopausal patients with breast cancer from the 1950s until the introduction of the safer antioestrogen, tamoxifen in the 1970s. The anti-tumour mechanism of high dose oestrogen therapy remained unknown. There was no enthusiasm to study these signal transduction pathways as oestrogen therapy has almost completely been eliminated from the treatme Read More

Inflammatory signaling networks play critical roles in the interpretation and processing of external and internal challenges encountered by living organisms. Consequently, alterations in various inflammatory processes are linked with almost all human diseases, and provide important clues for potential pharmacological intervention. Macrophages and CD4 T helper cells are central modulators within the inflammatory network. B Read More

17β-Estradiol (E2) controls many aspects of human physiology, including development, reproduction and homeostasis, through regulation of the transcriptional activity of its cognate receptors (ERs). E2 induces profound, rapid effects on the conformation of ERs allowing them to dimerize and to translocate into the nucleus where specific hormone response elements present in DNA are recognized. ER-E2 complex can also func Read More

There is increasing evidence to support the idea that immune modulation is involved in cancer progression. Indeed, the growth in the number of publications describing cancer immunotherapy and how it impacts on cell signaling pathways reinforces this idea. In particular, the forkhead box P3 (Foxp3) transcription factor is an important protagonist in regulatory T cell (Treg) suppression, which has recently been reported to be m Read More

Protein phosphorylation catalyzed by protein kinases plays critical roles in the regulation of signal-transduction pathways. Deregulated kinase activity is observed in a variety of human diseases, such as cancer, making them targets for the development of molecular therapies. The PI3K/PTEN/AKT/mTOR and RAF/MEK/ERK signaling pathways play fundamental roles in transmitting signals from membrane receptors to Read More

Thyroid hormone (L-3,3,,5-triiodothyronine, T3) is important for the normal function of most tissues, with major actions on O2 consumption and metabolic rate. In the liver, these are due to (i) transcriptional activation of respiratory genes leading to increased reactive O2 species generation in mitochondria and other subcellular sites; and (ii) enhancement in the respiratory burst activity in Kupffer cells (KC), with consequent a Read More