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Results for “Signaling”

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At least 199 records · Page 11Linked to original sources

PubMed2002

Transmodulation of BCR signaling by transduction-incompetent antigen receptors: implications for impaired signaling in anergic B cells.

B cell tolerance can be maintained by functional inactivation, or anergy, wherein B cell Ag receptors (BCR) remain capable of binding Ag, but are unable to transduce signals. Although the molecular mechanisms underlying this unresponsiveness are unknown, some models of B cell anergy are characterized by disruption of proximal BCR signaling events, and by destabilization of the BCR complex. Receptor destabilization is manifest by a reduced ability to coimmunoprecipitate membrane Ig with the Ig-alpha/Ig-beta signal-transducing complex. To begin to explore the possibility that anergy is the consequence of receptor destabilization, we analyzed a panel of B lymphoma transfectants expressing constant amounts of signal-competent Ag receptors and varied amounts of a receptor with identical specificity, but bearing mutations that render it incapable of interacting with Ig-alpha/Ig-beta. This analysis revealed that coaggregation of signal-incompetent receptors prevented Ag-induced Ig-alpha and Syk phosphorylation, mobilization of Ca(2+), and the up-regulation of CD69 mediated by competent receptors. In contrast, Ag-induced Cbl and Erk phosphorylation were unaffected. Data indicate that coaggregation of destabilized receptors (as few as approximately 15% of total) with signal-competent receptors significantly affects the ability of competent receptors to transduce signals. Thus, BCR destabilization may underlie the Ag unresponsiveness of anergic B cells.

Animals↗

PubMed1999

Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling.

Mitogenic signal-transduction pathways have not been well defined in pancreatic beta-cells. In the glucose-sensitive rat beta-cell line, INS-1, glucose (6-18 mM) increased INS-1 cell proliferation (>20-fold at 15 mM glucose). Rat growth hormone (rGH) also induced INS-1 cell proliferation, but this was glucose-dependent in the physiologically relevant concentration range (6-18 mM glucose). The combination of rGH (10 nM) and glucose (15 mM) was synergistic, maximally increasing INS-1 cell proliferation by >50-fold. Moreover, glucose-dependent rGH-induced INS-1 cell proliferation was increased further by addition of insulin-like growth factor 1 (IGF-1; 10 nM) to >90-fold at 12 mM glucose. Glucose metabolism and phosphatidylinositol-3'-kinase (PI3'K) activation were necessary for both glucose- and rGH-stimulated INS-1 cell proliferation. Glucose (>3 mM) independently increased tyrosine-phosphorylation-mediated recruitment of growth-factor-bound protein 2 (Grb2)/murine sons of sevenless-1 protein (mSOS) and PI3'K to insulin receptor substrate (IRS)-1 and IRS-2, as well as SH2-containing protein (Shc) association with Grb2/mSOS and downstream activation of mitogen-activated protein kinase and 70 kDa S6 kinase. Glucose-induced IRS- and Shc-mediated signal transduction was enhanced further by the addition of IGF-1, but not rGH. In contrast, rGH was able to activate Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signal transduction at glucose concentrations above 3 mM, but neither glucose independently, nor glucose with added IGF-1, were able to activate the JAK2/STAT5 signalling pathway. Thus rGH-mediated proliferation of beta-cells is directly via the JAK2/STAT5 pathway without engaging the Shc or IRS signal-transduction pathways, although activation of PI3'K may play an important permissive role in the glucose-dependent aspect of rGH-induced beta-cell mitogensis. The additive effect of rGH and IGF-1 on glucose-dependent beta-cell proliferation is therefore reflective of rGH and IGF-1 activating distinctly different mitogenic signalling pathways in beta-cells with minimal crosstalk between them.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling.

OBJECTIVE: To determine whether hydralazine might decrease DNA methyltransferase (DNMT) expression and induce autoimmunity by inhibiting extracellular signal-regulated kinase (ERK) pathway signaling. METHODS: The effect of hydralazine on DNMT was tested in vitro using enzyme inhibition studies, and in vivo by measuring messenger RNA (mRNA) levels and enzyme activity. Effects on ERK, c-Jun N-terminal kinase, and p38 pathway signaling were tested using immunoblotting. Murine T cells treated with hydralazine or an ERK pathway inhibitor were injected into mice and anti-DNA antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: In vitro, hydralazine did not inhibit DNMT activity. Instead, hydralazine inhibited ERK pathway signaling, thereby decreasing DNMT1 and DNMT3a mRNA expression and DNMT enzyme activity similar to mitogen-activated protein kinase kinase (MEK) inhibitors. Inhibiting T cell ERK pathway signaling with an MEK inhibitor was sufficient to induce anti-double-stranded DNA antibodies in a murine model of drug-induced lupus, similar to the effect of hydralazine. CONCLUSION: Hydralazine reproduces the lupus ERK pathway signaling abnormality and its effects on DNMT expression, and inhibiting this pathway induces autoimmunity. Hydralazine-induced lupus could be caused in part by inducing the same ERK pathway signaling defect that occurs in idiopathic lupus.

Animals↗

PubMed1995

A new type of signal peptide: central role of a twin-arginine motif in transfer signals for the delta pH-dependent thylakoidal protein translocase.

The delta pH-driven and Sec-related thylakoidal protein translocases recognise distinct types of thylakoid transfer signal, yet all transfer signals resemble bacterial signal peptides in structural terms. Comparison of known transfer signals reveals a single concrete difference: signals for the delta pH-dependent system contain a common twin-arginine motif immediately before the hydrophobic region. We show that this motif is critical for the delta pH-driven translocation process; substitution of the arg-arg by gln-gln or even arg-lys totally blocks translocation across the thylakoid membrane, and replacement by lys-arg reduces the rate of translocation by > 100-fold. The targeting information in this type of signal thus differs fundamentally from that of bacterial signal peptides, where the required positive charge can be supplied by any basic amino acid. Insertion of a twin-arg motif into a Sec-dependent substrate does not alter the pathway followed but reduces translocation efficiency, suggesting that the motif may also repel the Sec-type system. Other information must help to specify the choice of translocation mechanism, but this information is unlikely to reside in the hydrophobic region because substitution by a hydrophobic section from an integral membrane protein does not affect the translocation pathway.

Amino Acid Sequence↗

PubMed2003

Parsing local signal evolution directly from a single-shot MRI signal: a new approach for fMRI.

In this work a new single-shot MRI method, single-shot parameter assessment by retrieval from signal encoding (SS-PARSE), is introduced. This method abandons a fundamental simplifying assumption that is used in conventional MRI methods. Established MRI methods implicitly assume that the local intrinsic signal does not change its amplitude or phase during signal acquisition, even though these changes may be substantial, especially during the relatively long signals used in single-shot image acquisitions. SS-PARSE, on the other hand, acknowledges local decay and phase evolution, and models each signal datum as a sample from (k,t)-space rather than k-space. Because of this more accurate signal model, SS-PARSE promises improved performance in terms of accuracy and robustness, but requires more intensive reconstruction computations. The theoretical properties of the method are discussed, and simulation results are presented that demonstrate more robust and accurate measurements of relaxation rate changes associated with brain activation in functional MRI (fMRI), freedom from geometric errors due to off-resonance frequencies, and better tolerance of the large susceptibility gradients that occur naturally in parts of the brain. In addition, this technique has the potential to assess nonexponential relaxation behavior during a single-shot signal.

Algorithms↗

PubMed1998

Differential regulation of extracellular signal-regulated kinase and nuclear factor-kappa B signal transduction pathways by hydrogen peroxide and tumor necrosis factor.

Reactive oxygen metabolites are increasingly recognized for their ability to stimulate signal transduction pathways. This is important because these oxidants are frequently generated at sites of inflammation. However, little is known about the manner in which reactive oxygen species may selectively stimulate distinct signaling pathways. We have examined this question by stimulating mesothelial cells with hydrogen peroxide (H2O2) as a model oxidant stimulus. The response to H2O2 was examined by measuring the activation of the extracellular signal-regulated kinase (ERK1/2) and the nuclear factor-kappa B (NF-kappa B) signal transduction pathways. We found that H2O2 stimulated activity of the ERK1/2 pathway in a dose- and time-dependent manner. The ability of H2O2 to activate ERK1/2 was similar to that found with tumor necrosis factor (TNF) stimulation. The oxidant effect was inhibited by various reactive oxygen scavengers. An inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase, the upstream kinase that activates ERK1/2, inhibited the oxidant effect. The superoxide anion (O2-) also stimulated ERK1/2 activity. In contrast, H2O2 did not stimulate proteolysis of I kappa B-alpha and induced only a small degree of NF-kappa B nuclear translocation. Stimulation of the cells with O2- also induced a minimal degree of NF-kappa B activation. TNF was a potent stimulus for I kappa B-alpha proteolysis and NF-kappa B activation, demonstrating that the cells did have a functional NF-kappa B pathway. These results suggest that oxidants may selectively stimulate certain pathways, thereby preserving some specificity of the signaling process. Furthermore, different cell types and distinct signaling pathways within cells may demonstrate unique profiles in the manner in which they respond to oxidant stimulation.

Animals↗

PubMed1992

New signal processing techniques for the decomposition of EMG signals.

This paper relates to the use of knowledge-based signal processing techniques in the decomposition of EMG signals. The aim of the research is to automatically decompose EMG signals recorded at force levels up to 20 per cent maximum voluntary contraction (MVC) into their constituent motor unit action potentials (MUAPS), and to display the MUAP shapes and firing times for the clinician. This requires the classification of nonoverlapping MUAPs and superimposed waveforms formed from overlapping MUAPs in the signal. Nonoverlapping MUAPs are classified using a statistical pattern-recognition method. The decomposition of superimposed waveforms uses a combination of procedural and knowledge-based methods. The decomposition method was tested on real and simulated EMG data recorded at force levels up to 20 per cent MVC. The different EMG signals contained up to six motor units (MUs). The new decomposition program classifies the total number of MUAP firings in an EMG signal with an accuracy always greater than 95 per cent. The decomposition program takes about 15s to classify all nonoverlapping MUAPs in EMG signal of length 1.0s and, on average, an extra 9s to classify each superimposed waveform.

Action Potentials↗

PubMed2005

Optimum signal in a simple neuronal model with signal-dependent noise.

How does the information about a signal in neural threshold crossings depend on the noise acting upon it? Two models are explored, a binary McCulloch and Pitts (threshold exceedance) model and a model of waiting time to exceedance--a discrete-time version of interspike intervals. If noise grows linearly with the signal, we find the best identification of the signal in terms of the Fisher information is for signals that do not reach the threshold in the absence of noise. Identification attains the same precision under weak and strong signals, but the coding range decreases at both extremes of signal level. We compare the results obtained for Fisher information with those using related first and second moment measures. The maximum obtainable information is plotted as a function of the ratio of noise to signal.

Action Potentials↗

PubMed2005

Effects of stop-signal modality on the N2/P3 complex elicited in the stop-signal paradigm.

The principal aim of the present study was to clarify how stop-signal modality affected the speed and efficacy of stopping, using ERP components as converging measures of stop processes. Both performance and ERP latency findings suggested faster processing of stop signals in the auditory than visual version of the stop task. The effects of successful versus unsuccessful stopping on the amplitude and topography of N2/P3 components elicited by the stop signals appeared to be largely independent of the modality of the stop signals. Stop signals elicited a fronto-central N2 that was much larger on unsuccessful than successful stop trials in stimulus-locked waveforms. N2 was followed by a P3 component that showed a fronto-central distribution on successful stop trials. P3 elicited on unsuccessful stop trials showed a posterior-parietal focus, but this topography was manifested more clearly in response-locked than stimulus-locked waveforms. A dipole source analyses confirmed these topographical differences of P3, and further showed that the location of the corresponding dipoles remained largely identical across the visual and auditory versions of the stop-signal task. Taken together, the present findings support the suggestion that ERP components in the stop task reflect endogenous aspects of stop-signal processing, such as effective inhibition of responses on successful stop trials and detection of errors on failed inhibition trials.

Adult↗

PubMed2006

Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signals.

The intramembrane-cleaving proteases (I-CLiPs) presenilin-1 and -2 (PS1 and PS2), signal peptide peptidase (SPP) and the Site-2 protease (S2P) catalyze critical steps in cell signaling and are implicated in diseases such as Alzheimer's disease, hepatitis C virus (HCV) infection and cholesterol homeostasis. Here we describe the development of a cellular assay based on cleavage of the transmembrane sequence of the HCV core protein precursor, releasing intra- and extra-cellular signals that represent sequential signal peptidase and SPP cleavage, respectively. We find that the SPP inhibitor (Z-LL)2-ketone (IC50 = 1.33 microM) and the gamma-secretase potent inhibitors NVP-AHW700-NX (IC50 = 51 nM) and LY411575 (IC50 = 61 nM) but not DAPT dose dependently inhibited SPP but not signal peptidase cleavage. Our data confirm that type II orientated substrates, like the HCV transmembrane sequence, are sequentially cleaved by signal peptidase then SPP. This dual assay provides a powerful tool to pharmacologically analyze sequential cleavage events of signal peptidase and SPP and their regulation.

Amino Acid Sequence↗

PubMed2003

The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling.

Normal cardiovascular development and physiology depend in part upon signalling through G-protein-coupled receptors (GPCRs), such as the angiotensin II type 1 (AT(1)) receptor, sphingosine 1-phosphate (S1P) receptors and endothelin-1 (ET-1) receptor. Since regulator of G-protein signalling (RGS) proteins function as GTPase-activating proteins for the G alpha subunit of heterotrimeric G-proteins, these proteins undoubtedly have functional roles in the cardiovascular system. In the present paper, we show that human aorta and heart differentially express RGS1, RGS2, RGS3S (short-form), RGS3L (long-form), PDZ-RGS3 (PDZ domain-containing) and RGS4. The aorta prominently expresses mRNAs for all these RGS proteins except PDZ-RGS3. Various stimuli that are critical for both cardiovascular development and function regulate dynamically the mRNA levels of several of these RGS proteins in primary human aortic smooth muscle cells. Both RGS1 and RGS3 inhibit signalling through the S1P(1) (formerly known as EDG-1), S1P(2) (formerly known as EDG-5) and S1P(3) (formerly known as EDG-3) receptors, whereas RGS2 and RGS4 selectively attenuate S1P(2)-and S1P(3)-receptor signalling respectively. All of the tested RGS proteins inhibit AT(1)-receptor signalling, whereas only RGS3 and, to a lesser extent, RGS4 inhibit ET(A)-receptor signalling. The conspicuous expression of RGS proteins in the cardiovascular system and their selective effects on relevant GPCR-signalling pathways provide additional evidence that they have functional roles in cardiovascular development and physiology.

Angiotensin II↗

PubMed1997

Logical analysis of timing-dependent receptor signalling specificity: application to the insulin receptor metabolic and mitogenic signalling pathways.

We present a method for logical analysis of signal-transduction networks, focusing on metabolic and mitogenic signalling by the insulin receptor, with specific emphasis on dependence of the signalling properties on the timing of binding events. We discuss a basic model which demonstrates this dependence (hormone binding leads to activation of the receptor which can lead to a commitment to mitogenic signalling), and show how residence time of the hormone on the receptor can determine the specificity of signalling between the alternative metabolic or mitogenic pathways. The method gives conditions for the selection of specific branches in the signalling pathway expressed in terms of inequalities among the characteristic activation or deactivation times of components of that pathway. In this way, the conditions for mitogenic signalling can be given in terms of a required range of values of the hormone residence time on the receptor, which is directly related to the kinetic dissociation rate.

Animals↗

PubMed2000

Activation of intracellular signaling by hepatitis B and C viruses: C-viral core is the most potent signal inducer.

To clarify the effects of hepatitis C virus (HCV) infection on hepatocytes, we analyzed and compared the induction of intracellular signals by HCV and hepatitis B virus (HBV) proteins. We examined the influence of 7 HCV (core, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) and 4 HBV (precore, core, polymerase, and X) proteins on 5 well-defined intracellular signaling pathways associated with cell proliferation, differentiation, and apoptosis by use of a reporter assay. Viral protein-expression vectors were cotransfected into mammalian cells with reporter vectors having a luciferase gene driven by the following inducible cis-enhancer elements: the cyclic adenosine monophosphate response element, the serum response element (SRE), and the binding sites for nuclear factor kappaB (NF-kappaB), activator protein 1 (AP-1), and serum response factor (SRF). In addition, the activation of signals by HCV proteins was examined in a reporter plasmid having a natural interleukin-8 (IL-8) promoter upstream of a luciferase gene. Of 11 HCV and HBV proteins, HCV core had the strongest influence on intracellular signals, especially NF-kappaB-, AP-1-, and SRE-associated pathways. HCV core's activation level exceeded that of HBV X protein, a well-characterized transactivator of these signals. Moreover, HCV core activated the IL-8 promoter through NF-kappaB and AP-1. For the other proteins, HCV NS4B showed signal activation, but signals were activated at a lesser extent. The luciferase reporter assay, a recently introduced technique, helped in the elucidation of molecular events underlying the inflammatory and proliferation process in the liver induced by HCV.

Blotting, Western↗

PubMed2004

Noisy signal amplification in ultrasensitive signal transduction.

Because intracellular processes are inherently noisy, stochastic reactions process noisy signals in cellular signal transduction. One essential feature of biological signal transduction systems is the amplification of small changes in input signals. However, small random changes in the input signals could also be amplified, and the transduction reaction can also generate noise. Here, we show theoretically how the abrupt response of ultrasensitive signal-transduction reactions results in the generation of large inherent noise and the high amplification of input noise. The inherently generated noise propagates with amplification through intracellular molecular network. We discuss how the contribution of such transmitted noise can be shown experimentally. Our results imply that the switch-like behavior of signal transduction could be limited by noise; however, high amplification reaction could be advantageous to generate large noise, which would be essential to maintain behavioral variability.

Gene Expression↗

PubMed2006

Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules.

Wnt signaling is essential for T cell development in the thymus, but the stages in which it occurs and the molecular mechanisms underlying Wnt responsiveness have remained elusive. Here we examined Wnt signaling activity in both human and murine thymocyte populations by determining beta-catenin levels, Tcf-reporter activation and expression of Wnt-target genes. We demonstrate that Wnt signaling occurs in all thymocyte subsets, including the more mature populations, but most prominently in the double negative (DN) subsets. This differential sensitivity to Wnt signaling was not caused by differences in the presence of Wnts or Wnt receptors, as these appeared to be expressed at comparable levels in all thymocyte subsets. Rather, it can be explained by high expression of activating signaling molecules in DN cells, e.g., beta-catenin, plakoglobin, and long forms of Tcf-1, and by low levels of inhibitory molecules. By blocking Wnt signaling from the earliest stage onwards using overexpression of Dickkopf, we show that inhibition of the canonical Wnt pathway blocks development at the most immature DN1 stage. Thus, responsiveness to developmental signals can be regulated by differential expression of intracellular mediators rather than by abundance of receptors or ligands.

Cell Differentiation↗

PubMed2001

Membrane proximal ERK signaling is required for M-calpain activation downstream of epidermal growth factor receptor signaling.

Localization of signaling is critical in directing cellular outcomes, especially in pleiotropic signaling pathways. The extracellular signal-regulated kinase (ERK)/microtubule-associated protein kinase, which promotes cell migration, proliferation, and differentiation is found in the nucleus and throughout the cytoplasm. Recently, it has been shown that nuclear translocation of ERK is required for transcriptional changes and cell proliferation. However, the cellular consequences, of cytoplasmic signaling have not been defined. We explored whether cytoplasmic, specifically membrane-proximal, ERK signaling is involved in growth factor-induced cell motility. We previously have demonstrated that increased M-calpain activity downstream of epidermal growth factor receptor (EGFR)-mediated ERK activation is necessary for epidermal growth factor (EGF)-induced motility. Calpain isoforms also have been found in nuclear, cytosolic, and plasma membrane-associated compartments in a variety of cell types. We now employ cell engineering approaches to control localization of the upstream EGFR and ERK activities to examine the spatial effect of upstream signal locale on downstream calpain activity. With differential ligand-induced internalization and trafficking-restricted receptor variants, we find that calpain activity is triggered only by plasma membrane-restricted activated EGFR, not by internalized (although still active) EGFR. Cells transfected with membrane-targeted ERK1 and ERK2, which sequester endogenous ERKs, exhibited normal EGF-induced calpain activity. Transfection of an inactive ERK phosphatase (MKP-3/Pyst1) that sequesters ERK in the cytoplasm prevented calpain activation as well as de-adhesion. These data strongly suggest that EGF-induced calpain activity can be enhanced near sites of membrane-proximal EGFR-mediated ERK signaling, providing insights about how calpain activity might be regulated and targeted to enhance its effects on adhesion-related substrates.

Animals↗

PubMed2003

Signal recognition particle binds to ribosome-bound signal sequences with fluorescence-detected subnanomolar affinity that does not diminish as the nascent chain lengthens.

The binding of signal recognition particle (SRP) to ribosome-bound signal sequences has been characterized directly and quantitatively using fluorescence spectroscopy. A fluorescent probe was incorporated cotranslationally into the signal sequence of a ribosome.nascent chain complex (RNC), and upon titration with SRP, a large and saturable increase in fluorescence intensity was observed. Spectral analyses of SRP and RNC association as a function of concentration allowed us to measure, at equilibrium, K(d) values of 0.05-0.38 nm for SRP.RNC complexes with different signal sequences. Competitive binding experiments with nonfluorescent RNC species revealed that the nascent chain probe did not alter SRP affinity and that SRP has significant affinity for both nontranslating ribosomes (K(d) = 71 nm) and RNCs that lack an exposed signal sequence (K(d) = 8 nm). SRP can therefore distinguish between translating and nontranslating ribosomes. The very high signal sequence-dependent SRP.RNC affinity did not decrease as the nascent chain lengthened. Thus, the inhibition of SRP-dependent targeting of RNCs to the endoplasmic reticulum membrane observed with long nascent chains does not result from reduced SRP binding to the signal sequence, as widely thought, but rather from a subsequent step, presumably nascent chain interference of SRP.RNC association with the SRP receptor and/or translocon.

Animals↗

PubMed2004

Role of regulator of G protein signaling 2 (RGS2) in Ca(2+) oscillations and adaptation of Ca(2+) signaling to reduce excitability of RGS2-/- cells.

Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Galpha subunits to determine the duration of the stimulated state and control G protein-coupled receptor-mediated cell signaling. RGS2 is an RGS protein that shows preference toward Galpha(q). To better understand the role of RGS2 in Ca(2+) signaling and Ca(2+) oscillations, we characterized Ca(2+) signaling in cells derived from RGS2(-/-) mice. Deletion of RGS2 modified the kinetic of inositol 1,4,5-trisphosphate (IP(3)) production without affecting the peak level of IP(3), but rather increased the steady-state level of IP(3) at all agonist concentrations. The increased steady-state level of IP(3) led to an increased frequency of [Ca(2+)](i) oscillations. The cells were adapted to deletion of RGS2 by reducing Ca(2+) signaling excitability. Reduced excitability was achieved by adaptation of all transporters to reduce Ca(2+) influx into the cytosol. Thus, IP(3) receptor 1 was down-regulated and IP(3) receptor 3 was up-regulated in RGS2(-/-) cells to reduce the sensitivity for IP(3) to release Ca(2+) from the endoplasmic reticulum to the cytosol. Sarco/endoplasmic reticulum Ca(2+) ATPase 2b was up-regulated to more rapidly remove Ca(2+) from the cytosol of RGS2(-/-) cells. Agonist-stimulated Ca(2+) influx was reduced, and Ca(2+) efflux by plasma membrane Ca(2+) was up-regulated in RGS2(-/-) cells. The result of these adaptive mechanisms was the reduced excitability of Ca(2+) signaling, as reflected by the markedly reduced response of RGS2(-/-) cells to changes in the endoplasmic reticulum Ca(2+) load and to an increase in extracellular Ca(2+). These findings highlight the central role of RGS proteins in [Ca(2+)](i) oscillations and reveal a prominent plasticity and adaptability of the Ca(2+) signaling apparatus.

Adaptation, Physiological↗