Microtubules and signal transduction

Although molecular components of signal transduction pathways are rapidly being identified, how elements of these pathways are positioned spatially and how signals traverse the intracellular environment from the cell surface to the nucleus or to other cytoplasmic targets are not well understood. The discovery of signaling molecules that interact with microtubules (MTs), as well as the multiple effects on signaling pathways of drugs that destabilize or hyperstabilize MTs, indicate that MTs are likely to be critical to the spatial organization of signal transduction. MTs themselves are also affected by signaling pathways and this may contribute to the transmission of signals to downstream targets.     

Oxygen signal transduction

Although manifestations of O2 adaptation have long been examined, only now are biochemical mechanisms of O2 regulation beginning to be understood. This article comments on the current state of knowledge about proteins that function as direct sensors of molecular oxygen and makes predictions about as yet undiscovered sensors.     

VEGF-receptor signal transduction

The vascular endothelial growth factor (VEGF) family of ligands and receptors has been the focus of attention in vascular biology for more than a decade. There is now a consensus that the VEGFs are crucial for vascular development and neovascularization in physiological and pathological processes in both embryo and adult. This has facilitated a rapid transition to their use in clinical applications, for example, administration of VEGF ligands to enhance vascularization of ischaemic tissues and, conversely, inhibitors of VEGF-receptor function in anti-angiogenic therapy. More recent data indicate essential roles for the VEGFs in haematopoietic cell function and in lymphangiogenesis.     

ABA signal transduction

Recent advances in the study of abscisic acid signal transduction include the identification of cyclic ADP-ribose as a central mediator of abscisic acid responses. The characterisation of type 2C protein phosphatases, ABI1 and ABI2, implicates negative control and redundant action on the signal pathway of this hormone. In addition, abscisic acid-mediated inhibition of gibberellin-stimulated responses seems to depend on the activation of a phospholipase D during induction of alpha-amylase in barley aleurone cells as well as on a putative acetyltransferase involved in elongation growth.     

Gibberellin signal transduction

Recent studies using biochemical and genetic approaches have identified a number of components, including several negative regulators, of the gibberellin (GA) signal transduction pathway in higher plants. The basal state of GA signaling is likely to be repressive, and the GA signal seems to activate the pathway by de-repression to allow GA-stimulated growth and development.     

Lymphokine signal transduction

Lymphokines are a group of signalling molecules involved in communication between cells, mainly those of the immune system. The lymphokines are multi-functional and most of them have mitogenic or co-mitogenic activity. An understanding of lymphokine biology is essential to understand how the immune system develops and functions and to provide a rationale for their use in immunotherapy.The potential to understand the cell biology of the lymphokines has recently become more apparent as molecular biological techniques have first of all produced recombinant factors and secondly have provided clues to the signal transduction pathways by cloning receptors, applying site-directed mutational analysis and also probing for specific promoters and enhancers that are activated along the signal pathway.This review discusses the information that has come from these recent analyses which blends with the biochemical analysis of the second messenger systems in an effort to understand the signalling pathways of the lymphokines.     

Redox-dependent signal transduction

Reactive oxygen species (ROS) such as superoxide anions and hydrogen peroxide appear to be transiently produced in response to growth factor and cytokine stimulation. A variety of evidence suggests that this ligand-stimulated change in the cellular redox state participates in downstream signal transduction. This review will focus on the effects of ROS on signal transduction pathways, the molecules that regulate intracellular ROS production and the potential protein targets of oxidants.     

Cytokine receptors and signal transduction

Cytokines are important regulators of hemopoiesis which exert their actions by binding to specific, high affinity, cell surface receptors. In the past several years, molecular cloning of these receptors has revealed a new superfamily referred to as the hemopoietic growth factor receptors. Members of this family are defined by a 200 amino acid conserved domain; however, it has become increasingly apparent that another characteristic of these receptors is the shared usage of a common signalling subunit among subgroups in this family. The shared signalling component explains the functional redundancy of many cytokines; however, the mechanism by which these receptors transduce a signal across the membrane is not yet clear. Studies into cytokine action have shown that many of the events that occur in response to ligand stimulation are similar to those observed for the better characterized intrinsic tyrosine kinase receptors. Thus, although the cytokine receptors do not possess intrinsic tyrosine kinase activity, these observations have led to a model of cytokine signal transduction adapted from the signalling mechanisms described for the tyrosine kinase receptors.     

Oxysterols and calcium signal transduction

Ionised calcium (Ca²⁺) is a key second messenger, regulating almost every cellular process from cell death to muscle contraction. Cytosolic levels of this ion can be increased via gating of channel proteins located in the plasma membrane, endoplasmic reticulum and other membrane-delimited organelles. Ca²⁺ can be removed from cells by extrusion across the plasma membrane, uptake into organelles and buffering by anionic components. Ca²⁺ channels and extrusion mechanisms work in concert to generate diverse spatiotemporal patterns of this second messenger, the distinct profiles of which determine different cellular outcomes. Increases in cytoplasmic Ca²⁺ concentration are one of the most rapid cellular responses upon exposure to certain oxysterol congeners or to oxidised low-density lipoprotein, occurring within seconds of addition and preceding increases in levels of reactive oxygen species, or changes in gene expression. Furthermore, exposure of cells to oxysterols for periods of hours to days modulates Ca²⁺ signal transduction, with these longer-term alterations in cellular Ca²⁺ homeostasis potentially underlying pathological events within atherosclerotic lesions, such as hyporeactivity to vasoconstrictors observed in vascular smooth muscle, or ER stress-induced cell death in macrophages. Despite their candidate roles in physiology and disease, little is known about the molecular mechanisms that couple changes in oxysterol concentrations to alterations in Ca²⁺ signalling. This review examines the ways in which oxysterols could influence Ca²⁺ signal transduction and the potential roles of this in health and disease.