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Results for “Signaling crosstalk”

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At least 19 recordsLinked to original sources
PubMed1999

Regulation of Smad signalling by protein associations and signalling crosstalk.

Smads are intracellular signalling mediators for the family of transforming growth factor beta (TGF-beta)-related growth and differentiation factors, which signal through transmembrane serine/threonine kinases. Following receptor-induced activation, heteromeric Smad complexes translocate into the nucleus, where they act as transcription factors. Recent progress has revealed that Smad signalling is not merely determined by activation of the class of TGF-beta receptors, but is also regulated through crosstalk with other kinase signalling cascades. In addition, the Smads regulate transcription through functional cooperativity and physical interactions with other transcription factors, which might also be targets for regulation by other signalling cascades. This signalling crosstalk might explain the complexity of the responses to TGF-beta and related factors.

Animals↗
PubMed2002

Signaling crosstalk between RANKL and interferons in osteoclast differentiation.

Regulation of osteoclast differentiation is an aspect central to the understanding of the pathogenesis and the treatment of bone diseases such as autoimmune arthritis and osteoporosis. In fact, excessive signaling by RANKL (receptor activator of nuclear factor kappaB ligand), a member of the tumor necrosis factor (TNF) family essential for osteoclastogenesis, may contribute to such pathological conditions. Here we summarize our current work on the negative regulation of osteoclastogenesis by unique signaling crosstalk between RANKL and interferons (IFNs). First, activated T cells maintain bone homeostasis by counterbalancing the action of RANKL through production of IFN-gamma. This cytokine induces rapid degradation of the RANK (receptor activator of nuclear factor kappaB) adapter protein TRAF6 (TNF-receptor-associated factor 6), resulting in strong inhibition of the RANKL-induced activation of NF-kappaB and JNK (c-Jun N-terminal kinase). Second, RANKL induces the IFN-beta gene but not IFN-alpha genes, in osteoclast precursor cells, and that IFN-beta strongly inhibits the osteoclast differentiation by interfering with the RANKL-induced expression of c-Fos. The series of in vivo experiments revealed that these two distinct IFN-mediated regulatory mechanisms are both important to maintain homeostasis of bone resorption. Collectively, these studies revealed novel aspects of the two types of IFN, beyond their original roles in the immune response, and may offer a molecular basis for the treatment of bone diseases.

Animals↗
PubMed2003

Signalling crosstalk in plants: emerging issues.

The Oxford English Dictionary defines crosstalk as 'unwanted transfer of signals between communication channels'. How does this definition relate to the way in which we view the organization and function of signalling pathways? Recent advances in the field of plant signalling have challenged the traditional view of a signalling transduction cascade as isolated linear pathways. Instead the picture emerging of the mechanisms by which plants transduce environmental signals is of the interaction between transduction chains. The manner in which these interactions occur (and indeed whether the transfer of these signals is 'unwanted' or beneficial) is currently the topic of intense research.

Plant Physiological Phenomena↗
PubMed2005

Signal crosstalk and induced resistance: straddling the line between cost and benefit.

This review discusses recent progress in our understanding of signaling in induced plant resistance and susceptibility to pathogens and insect herbivores, with a focus on the connections and crosstalk among phytohormone signaling networks that regulate responses to these and other stresses. Multiple stresses, often simultaneous, reduce growth and yield in plants. However, prior challenge by a pathogen or insect herbivore also can induce resistance to subsequent challenge. This resistance, or failure of susceptibility, must be orchestrated within a larger physiological context that is strongly influenced by other biotic agents and by abiotic stresses such as inadequate light, temperature extremes, drought, nutrient limitation, and soil salinity. Continued research in this area is predicated on the notion that effective utilization of induced resistance in crop protection will require a functional understanding of the physiological consequences of the "induced" state of the plant, coupled with the knowledge of the specificity and compatibility of the signaling systems leading to this state. This information may guide related strategies to improve crop performance in suboptimal environments, and define the limits of induced resistance in certain agricultural contexts.

Agriculture↗
PubMed2006

Signaling crosstalk angiotensin II receptor subtypes and insulin.

Insulin-resistant states are often associated with hypertension, and the accumulated data indicate that ARB decrease new-onset of diabetes with vasoprotective effects. Recent evidence suggests that activation of Ang II receptor subtypes could regulate insulin sensitivity at multiple sites of insulin signaling in various diabetic animal models and regulate vascular remodeling in concert with insulin in potentially distinct fashions. Moreover, the roles of Ang II receptor subtypes have been highlighted in insulin resistance in obesity, which is one of the major risk factors for the development of hypertension. More detailed analysis of the crosstalk of Ang II and insulin-mediated signaling in various tissues would provide further information to understand the clinical relevance of the effect of ARB on insulin resistance, thereby preventing cardiovascular events associated with insulin resistance.

Angiotensin II↗
PubMed2005

Signalling crosstalk in FGF2-mediated protection of endothelial cells from HIV-gp120.

BACKGROUND: The blood brain barrier (BBB) is the first line of defence of the central nervous system (CNS) against circulating pathogens, such as HIV. The cytotoxic HIV protein, gp120, damages endothelial cells of the BBB, thereby compromising its integrity, which may lead to migration of HIV-infected cells into the brain. Fibroblast growth factor 2 (FGF2), produced primarily by astrocytes, promotes endothelial cell fitness and angiogenesis. We hypothesized that treatment of human umbilical vein endothelial cells (HUVEC) with FGF2 would protect the cells from gp120-mediated toxicity via endothelial cell survival signalling. RESULTS: Exposure of HUVEC to gp120 resulted in dose- and time-dependent cell death; whereas, pre-treatment of endothelial cells with FGF2 protected cells from gp120 angiotoxicity. Treatment of HUVEC with FGF2 resulted in dose- and time-dependent activation of the extracellular regulated kinase (ERK), with moderate effects on phosphoinositol 3 kinase (PI3K) and protein kinase B (PKB), also known as AKT, but no effects on glycogen synthase kinase 3 (GSK3beta) activity. Using pharmacological approaches, gene transfer and kinase activity assays, we show that FGF2-mediated angioprotection against gp120 toxicity is regulated by crosstalk among the ERK, PI3K-AKT and PKC signalling pathways. CONCLUSIONS: Taken together, these results suggest that FGF2 may play a significant role in maintaining the integrity of the BBB during the progress of HIV associated cerebral endothelial cell damage.

Animals↗
PubMed2002

Cytokine G-protein signaling crosstalk in cardiomyocytes: attenuation of Jak-STAT activation by endothelin-1.

The IL-6-related cytokines, LIF and cardiotrophin-1, are important growth promoting and cardioprotective agents for cardiomyocytes. However, factors that regulate their actions in the heart are poorly understood. In this study, we tested the hypothesis that endothelin-1, a peptide hormone that produces a pattern of cardiac hypertrophy distinct from LIF and cardiotrophin-1, modulates LIF-induced signaling in cardiomyocytes. Upon binding LIF or cardiotrophin-1, the LIF receptor alpha subunit (LIFRalpha) dimerizes with gp130, leading to activation of constitutively associated Jak1 proteins and LIFRalpha-gp130 tyrosine phosphorylation. We found that pretreatment of neonatal rat ventricular myocytes with endothelin-1 rapidly inhibited LIF-induced LIFRalpha tyrosine phosphorylation and Jak1 activation. This effect of endothelin-1 on LIFalpha and Jak1 was attenuated by the MEK1 inhibitor, PD98059, implicating involvement of the ERK kinases. Radioligand binding studies showed that inhibition of LIF signaling resulted from a reduction in cell surface LlFRalpha levels. Additionally, endothelin-1 was found to reduce LIF-induced STAT3 activation, as indexed by STAT3 Y705 phosphorylation. Finally, endothelin-1 and LIF were shown to induce opposite patterns of STAT3 activation in cardiomyocytes. LIF induced rapid, robust STAT3 Y705 phosphorylation; endothelin-1 produced a delayed, modest increase, and initially decreased STAT3 Y705 phosphorylation. Overall our findings indicate that endothelin-1 acts to temper IL-6-related cytokine signaling in cardiomyocytes, in particular STAT3 activation.

Animals↗
PubMed2001

Signaling crosstalk underlying synergistic induction of astrocyte differentiation by BMPs and IL-6 family of cytokines.

We here show that bone morphogenetic protein (BMP) 7 acted in synergy with the distinct type of cytokines, leukemia inhibitory factor (LIF) and interleukin (IL) 6 that are in the IL-6 family, to induce astrocyte differentiation from neuroepithelial cells as assessed by expression of glial fibrillary acidic protein (GFAP). In this synergistic action, transcription factors, Smads and STAT3 (for signal transducer and activator of transcription 3) activated by respective group of cytokines, as well as a transcriptional coactivator p300 were essential. Taken together with our previous finding that the synergistic astrocyte induction by BMP2 and LIF is attributed to the complex formation of Smads and STAT3 bridged by p300, it is conceivable that this complex formation is a mechanism utilized in common by two different types of cytokines belonging to the BMP and IL-6 families in order to synergistically induce astrocyte differentiation.

Animals↗
PubMed2005

Signal-crosstalk between Rho/ROCK and c-Jun NH2-terminal kinase mediates migration of vascular smooth muscle cells stimulated by angiotensin II.

BACKGROUND: Rho and its effector Rho-kinase/ROCK mediate cytoskeletal reorganization as well as smooth muscle contraction. Recent studies indicate that Rho and ROCK are critically involved in vascular remodeling. Here, we tested the hypothesis that Rho/ROCK are critically involved in angiotensin II (Ang II)-induced migration of vascular smooth muscle cells (VSMCs) by mediating a specific signal cross-talk. METHODS AND RESULTS: Immunoblotting demonstrated that Ang II stimulated phosphorylation of a ROCK substrate, regulatory myosin phosphatase targeting subunit (MYPT)-1. Phosphorylation of MYPT-1 as well as migration of VSMCs induced by Ang II was inhibited by dominant-negative Rho (dnRho) or ROCK inhibitor, Y27632. Ang II-induced c-Jun NH2-terminal kinase (JNK) activation, but extracellular signal-regulated kinase (ERK) activation was not mediated through Rho/ROCK. Thus, infection of adenovirus encoding dnJNK inhibited VSMC migration by Ang II. We have further demonstrated that the Rho/ROCK activation by Ang II requires protein kinase C-delta (PKCdelta) and proline-rich tyrosine kinase 2 (PYK2) activation, but not epidermal growth factor receptor transactivation. Also, VSMCs express PDZ-Rho guanine nucleotide exchange factor (GEF) and Ang II stimulated PYK2 association with tyrosine phosphorylated PDZ-RhoGEF. CONCLUSIONS: PKCdelta/PYK2-dependent Rho/ROCK activation through PDZ-RhoGEF mediates Ang II-induced VSMC migration via JNK activation in VSMCs, providing a novel mechanistic role of the Rho/ROCK cascade that is involved in vascular remodeling.

Adenoviridae↗
PubMed2006

p38gamma mitogen-activated protein kinase integrates signaling crosstalk between Ras and estrogen receptor to increase breast cancer invasion.

Ras is believed to stimulate invasion and growth by different effector pathways, and yet, the existence of such effectors under physiologic conditions has not been shown. Estrogen receptor (ER), on the other hand, is both anti-invasive and proliferative in human breast cancer, with mechanisms for these paradoxical actions remaining largely unknown. Our previous work showed an essential role of p38gamma mitogen-activated protein kinase in Ras transformation in rat intestinal epithelial cells, and here, we show that p38gamma integrates invasive antagonism between Ras and ER to increase human breast cancer invasion without affecting their proliferative activity. Ras positively regulates p38gamma expression, and p38gamma in turn mediates Ras nonmitogenic signaling to increase invasion. Expression of the Ras/p38gamma axis, however, is trans-suppressed by ER that inhibits invasion and stimulates growth also by distinct mechanisms. Analysis of ER and its cytoplasmic localized mutant reveals that ER additionally binds to p38gamma protein, leading to its specific down-regulation in the nuclear compartment. A p38gamma-antagonistic activity of ER was further shown in a panel of breast cancer cell lines and was shown independent of estrogens by both ER depletion and ER expression. These results revealed that both Ras and ER use distinct pathways to regulate breast cancer growth and invasion, and that p38gamma specifically integrates their antagonistic activity to stimulate cell invasion. Selective targeting of p38gamma-dependent invasion pathways may be a novel strategy to control breast cancer progression.

Breast Neoplasms↗
PubMed2026

CaCl2 Priming Boosts Salinity-Alkalinity Tolerance in Germinating Soybean by Reducing DNA Oxidative Damage and Enhancing Ca2+ -ROS Signaling Crosstalk.

Soybean (Glycine max) seed germination is highly sensitive to saline-alkaline stress. Seed priming represents an effective strategy to mitigate its detrimental effects. However, the optimal priming conditions (agent, concentration, duration) and the underlying molecular mechanisms remain poorly understood. This study investigated the effects of priming with distilled water (Control), calcium chloride (CaCl2), melatonin (MT), and proline (Pro) under saline-alkaline stress on soybean seed germination and the molecular basis of enhanced tolerance. Evaluation of ten germination-related parameters revealed that priming with 100 mM CaCl2 for 12 h significantly enhanced the germination rate. Physiological analyses demonstrated that CaCl2 priming effectively reduced reactive oxygen species (ROS) accumulation by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), while decreasing malondialdehyde (MDA) content. Furthermore, CaCl2 priming activated the Ca2+ signaling pathway by increasing radicle Ca2+ content and upregulating the expression levels of Ca2+ signaling-related genes (e.g., GmCAM7, GmCNGC2, GmCNGC19, GmMPK2, and GmMKK2). Additionally, CaCl2 priming significantly enhanced DNA damage repair capacity of soybean cultivars with differing saline-alkaline tolerance. This was manifested by reduced DNA oxidative damage and decreased random amplified polymorphic DNA (RAPD) polymorphism, thereby enhancing genomic stability and alleviating cell cycle arrest. These findings deepen our understanding of the complex regulatory role of calcium signaling in plant abiotic stress responses and provide important novel theoretical insights for improving crop resilience.

Glycine max↗
PubMed2004

Silencing of hydroperoxide lyase and allene oxide synthase reveals substrate and defense signaling crosstalk in Nicotiana attenuata.

The fatty acid hydroperoxide (HP) substrates required for the biosynthesis of jasmonic acid (JA) and green leaf volatiles (GLVs) are supplied by separate lipoxygenases (LOX). We silenced the expression of two genes downstream of the LOX: allene oxide synthase (AOS) and HP lyase (HPL) by antisense expression of endogenous genes (NaAOS, NaHPL) in Nicotiana attenuata, in which the biosynthesis of JA is amplified by herbivore-specific elicitors. We report that these elicitors also amplify wound-induced GLV releases, but suppress the wound-induced increase of NaHPL transcripts, suggesting that substrate flux controls GLV biosynthesis. As expected, silencing of NaHPL and NaAOS reduced GLV release and JA accumulation, respectively. Surprisingly, HPL- and AOS-silenced plants had enhanced JA and GLV responses, suggesting substrate 'crosstalk' between these two oxylipin cascades. Plants with depleted GLVs (as-hpl) were less attractive than wild type (WT) or empty vector control plants in choice-tests with native lepidopteran herbivores. In feeding trials, Manduca sexta larvae developed slower on as-hpl plants. The reduced larval consumption and performance, which was not caused by increases in defense responses in as-hpl plants, could be restored to WT levels by the addition of synthetic GLVs, demonstrating that GLVs function as feeding stimulants. Gene expression profiling by cDNA microarray analysis and characterization of several induced defenses in herbivore-elicited as-hpl and as-aos plants revealed differential involvement of JA and GLVs in defense signaling. Elicitation of volatile terpenoids (an indirect defense) requires JA signaling, where as trypsin protease inhibitor elicitation (a direct defense) requires both functional JA and GLV cascades.

Aldehyde-Lyases↗
PubMed2006

Production of reactive oxygen species and reactive nitrogen species by angiosperm stigmas and pollen: potential signalling crosstalk?

Angiosperm stigmas exhibit high levels of peroxidase activity when receptive to pollen. To explore possible function(s) of this peroxidase activity we investigated amounts of reactive oxygen species (ROS), particularly hydrogen peroxide, in stigmas and pollen. Because nitric oxide (NO) was recently implicated in pollen tube growth, we also investigated amounts of NO in pollen and stigmas. Reactive oxygen species accumulation was assessed with confocal microscopy and light microscopy using ROS probes DCFH2-DA and TMB, respectively. NO was assayed using the NO probe DAF-2DA and confocal microscopy. Stigmas from various different angiosperms were found to accumulate ROS, predominantly H2O2, constitutively. In Senecio squalidus and Arabidopsis thaliana high amounts of ROS/H2O2 were localized to stigmatic papillae. ROS/H2O2 amounts appeared reduced in stigmatic papillae to which pollen grains had adhered. S. squalidus and A. thaliana pollen produced relatively high amounts of NO compared with stigmas; treating stigmas with NO resulted in reduced amounts of stigmatic ROS/H2O2. Constitutive accumulation of ROS/H2O2 appears to be a feature of angiosperm stigmas. This novel finding is discussed in terms of a possible role for stigmatic ROS/H2O2 and pollen-derived NO in pollen-stigma interactions and defence.

Arabidopsis↗
PubMed2004

Topological analysis of mass-balanced signaling networks: a framework to obtain network properties including crosstalk.

Signal transduction networks have only been studied at a small scale because large-scale reconstructions and suitable in silico analysis methods have not been available. Since reconstructions of large signaling networks are progressing well there is now a need to develop a framework for analysing structural properties of signaling networks. One such framework is presented here, one that is based on systemically independent pathways and a mass-balanced representation of signaling events. This approach was applied to a prototypic signaling network and it allowed for: (1) a systemic analysis of all possible input/output relationships, (2) a quantitative evaluation of network crosstalk, or the interconnectivity of systemically independent pathways, (3) a measure of the redundancy in the signaling network, (4) the participation of reactions in signaling pathways, and (5) the calculation of correlated reaction sets. These properties emerge from network structure and can only be derived and studied within a defined mathematical framework. The calculations presented are the first of their kind for a signaling network, while similar analysis has been extensively performed for prototypic and genome-scale metabolic networks. This approach does not yet account for dynamic concentration profiles. Due to the scalability of the stoichiometric formalism used, the results presented for the prototypic signaling network can be obtained for large signaling networks once their reconstruction is completed.

Animals↗