Trophic cascades revealed in diverse ecosystems

New studies are documenting trophic cascades in theoretically unlikely systems such as tropical forests and the open ocean. Together with increasing evidence of cascades, there is a deepening understanding of the conditions that promote and inhibit the transmission of predatory effects. These conditions include the relative productivity of ecosystems, presence of refuges and the potential for compensation. However, trophic cascades are also altered by humans. Analyses of the extirpation of large animals reveal loss of cascades, and the potential of conservation to restore not only predator populations but also the ecosystem-level effects that ramify from their presence.     

Protein-protein interactions in signaling cascades

The process of signal transduction is dependent on specific protein-protein interactions. In many cases these interactions are mediated by modular protein domains that confer specific binding activity to the proteins in which they are found. Rapid progress has been made in the biochemical characterization of binding interactions, the identification of binding partners, and determination of the three-dimensional structures of binding modules and their ligands. The resulting information establishes the logical framework for our current understanding of the signal transduction machinery. In this overview a variety of protein interaction modules are discussed, and issues relating to binding specificity and the significance of a particular interaction are considered.     

On sensitivity amplification in intracellular signaling cascades

Sensitivity amplification has long been regarded as a virtually universal property of signal transduction cascades, yet a comprehensive parameter analysis remains a challenge even for relatively simple networks. We use a fast and accurate method to compute properties of multilevel cascades of activation-inactivation cycles and show that the monocyclic cascades amplify sensitivity only under specific conditions. In particular, it is found that efficient sensitivity amplification in a cascade, relative to the sensitivities of individual cycles, requires asymmetry in saturation of converter enzymes, with inhibitors much more saturated than activators.     

Prion protein induced signaling cascades in monocytes

Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP(C)), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP(C) fusion proteins synthesized with a human Fc-tag. PrP(C) fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK(1,2) and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP(C) in monocytes and macrophages.     

Protein kinase signaling cascades in CNS trauma

Advances in our understanding of the signaling pathways and cellular functions regulated by protein kinase cascades have paved the way to study their role in the response of brain and spinal cord to traumatic injury. Mechanical forces imparted by trauma stimulate mitogen-activated protein kinases and protein kinase B/Akt as well as cause changes in the state of phosphorylation of glycogen synthase kinase-3beta. Extracellular ATP released by mechanical strain stimulates P2 purinergic receptors that are coupled to these protein kinase signaling pathways. These kinases regulate gene expression, cell survival, proliferation, differentiation, growth arrest, and apoptosis, thereby affecting cell fate, repair and plasticity after trauma. Elucidation of the molecular responses of protein kinase cascades to mechanical strain and the genes regulated by these signaling pathways may lead to therapeutic opportunities to minimize losses in motor skills and cognitive function caused by trauma to the central nervous system.     

Attenuation of noise in ultrasensitive signaling cascades

Ultrasensitive cascades often implement thresholding operations in cell signaling and gene regulatory networks, converting graded input signals into discrete all-or-none outputs. However, the biochemical and genetic reactions involved in such cascades are subject to random fluctuations, leading to noise in output signal levels. Here we prove that cascades operating near saturation have output signal fluctuations that are bounded in magnitude, even as the number of noisy cascade stages becomes large. We show that these fluctuation-bounded cascades can be used to attenuate the noise in an input signal, and we find the optimal cascade length required to achieve the best possible noise reduction. Cascades with ultrasensitive transfer functions naturally operate near saturation, and can be made to simultaneously implement thresholding and noise reduction. They are therefore ideally suited to mediate signal transfer in both natural and artificial biological networks.     

Inflammatory signaling cascades and autophagy in cancer

Tumor-associated inflammation is predictive of poor prognosis and drives a variety of tumorigenic phenotypes, including tumor proliferation and survival, angiogenesis, invasiveness, and metastasis. Here, we review mammalian data addressing the interaction of macroautophagy/autophagy with key signaling cascades associated with tumor inflammation. Although our understanding of this area remains incomplete, certain inflammatory pathways have emerged as important mediators of the crosstalk between autophagy and inflammation in tumors. Consistent with the multifaceted roles for autophagy in tumor cells, results to date support the hypothesis that inflammatory pathways can suppress or induce autophagy in a context-dependent manner; in turn, autophagy suppresses or promotes inflammation in cancers. Furthermore, emerging data suggest that autophagy may influence cytokine production and secretion via diverse mechanisms, which has implications for the immune and inflammatory microenvironment in tumors.     

Behavioural ecology: hidden benefits revealed

In the cooperatively breeding superb fairy-wren, helpers have negligible effect on breeding success. So why help? The answer is hidden in the size of the eggs.     

A generic model for open signaling cascades with forward activation

In this work, cellular signal transduction in an open cascade with forward activation was studied. By proposing a generic model which captures the common features of major existing models in the literature, it is showed how signaling profile changes during the propagation along the cascade. In particular, a typical OFF-ON-OFF switch-like transient behavior with prolonged temporary ON state is revealed, where OFF and ON represent the states of low level and high level concentrations, respectively. Analytically this phenomenon is closely related to uniform convergence of the active protein concentration of downstream cycles in the finite time range and its failure in the entire time domain. Consequently a classification of open signaling cascade which can sustain OFF-ON-OFF behavior in the far downstream cycles is accessible. Relevant biological issues, such as delayed activation of downstream reaction cycles, signal amplification and prolonged signal duration, to the generic model is discussed.     

A link between the light and gibberellin signaling cascades.

In a recent issue of Cell, Salomé Prat and colleagues describe the characterization of PHOR1, an armadillo-related protein involved in gibberellin signaling and also responsive to light.     

The molecular puzzle of two-component signaling cascades

Two-component systems constitute prevalent signaling pathways in bacteria and mediate a large variety of adaptative cellular responses. Signaling proceeds through His-Asp phosphorelay cascades that involve two central partners, the histidine protein kinase and the response regulator protein. Structural studies have provided insights into some design principles and activation mechanisms of these multi-domain proteins implicated in the control of virulence gene expression in several pathogens.     

Long signaling cascades tend to attenuate retroactivity

Signaling pathways consisting of phosphorylation/dephosphorylation cycles with no explicit feedback allow signals to propagate not only from upstream to downstream but also from downstream to upstream due to retroactivity at the interconnection between phosphorylation/dephosphorylation cycles. However, the extent to which a downstream perturbation can propagate upstream in a signaling cascade and the parameters that affect this propagation are presently unknown. Here, we determine the downstream-to-upstream steady-state gain at each stage of the signaling cascade as a function of the cascade parameters. This gain can be made smaller than 1 (attenuation) by sufficiently fast kinase rates compared to the phosphatase rates and/or by sufficiently large Michaelis-Menten constants and sufficiently low amounts of total stage protein. Numerical studies performed on sets of biologically relevant parameters indicated that ∼50% of these parameters could give rise to amplification of the downstream perturbation at some stage in a three-stage cascade. In an n-stage cascade, the percentage of parameters that lead to an overall attenuation from the last stage to the first stage monotonically increases with the cascade length n and reaches 100% for cascades of length at least 6.     

Roles of mitogen-activated protein kinase cascades in ABA signaling

Abscisic acid (ABA) is a universal hormone in higher plants and plays a major role in various aspects of plant stress, growth, and development. Mitogen-activated protein kinase (MAPK) cascades are key signaling modules for responding to various extracellular stimuli in plants. The available data suggest that MAPK cascades are involved in some ABA responses, including antioxidant defense, guard cell signaling, and seed germination. Some MAPK phosphatases have also been demonstrated to be implicated in ABA responses. The goal of this review is to piece together the findings concerning MAPK cascades in ABA signaling. Questions and further perspectives of the roles played by MAPK cascades in ABA signaling are also furnished.