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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 469 records · Page 26
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

An engineered transforming growth factor β (TGF-β) monomer that functions as a dominant negative to block TGF-β signaling

The transforming growth factor β isoforms, TGF-β1, -β2, and -β3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor (TβRI) but dispensable for binding the other receptor required for TGF-β signaling, the TGF-β type II receptor (TβRII), as an alternative therapeutic modality for blocking TGF-β signaling in humans. As shown through binding studies and crystallography, the engineered monomer retained the same overall structure of native TGF-β monomers and bound TβRII in an identical manner. Cell-based luciferase assays showed that the engineered monomer functioned as a dominant negative to inhibit TGF-β signaling with a Ki of 20–70 nM. Investigation of the mechanism showed that the high affinity of the engineered monomer for TβRII, coupled with its reduced ability to non-covalently dimerize and its inability to bind and recruit TβRI, enabled it to bind endogenous TβRII but prevented it from binding and recruiting TβRI to form a signaling complex. In conclusion, such engineered monomers provide a new avenue to probe and manipulate TGF-β signaling and may inform similar modifications of other TGF-β family members.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Sensitivity of CTA to dark matter signals from the Galactic Center

The Galactic Center is one of the most promising targets for indirect detection of dark matter with gamma rays. We investigate the sensitivity of the upcoming Cherenkov Telescope Array (CTA) to dark matter annihilation and decay in the Galactic Center. As the inner density profile of the Milky Way's dark matter halo is uncertain, we study the impact of the slope of the Galactic density profile, inwards of the Sun, on the prospects for detecting a dark matter signal with CTA. Adopting the Ring Method to define the signal and background regions in an ON-OFF analysis approach, we find that the sensitivity achieved by CTA to annihilation signals is strongly dependent on the inner profile slope, whereas the dependence is more mild in the case of dark matter decay. Surprisingly, we find that the optimal choice of signal and background regions is virtually independent of the assumed density profile. For the fiducial case of a Navarro-Frenk-White profile, we find that CTA will be able to probe annihilation cross-sections well below the canonical thermal relic value for dark matter masses from a few tens of GeV up to ∼ 5 TeV for annihilation to τ{sup +}τ{sup −}, and will achieve only a slightly weaker sensitivity for annihilation to b b-bar or μ{sup +}μ{sup −}. CTA will improve significantly on current sensitivity to annihilation signals for dark matter masses above ∼ 100 GeV, covering parameter space that is complementary to that probed by searches with the Fermi Large Area Telescope. The interpretation of apparent excesses in the measured cosmic-ray electron and positron spectra as signals of dark matter decay will also be testable with CTA observations of the Galactic Center. We demonstrate that both for annihilation and for decay, including spectral information for hard channels (such as μ{sup +}μ{sup −} and τ{sup +}τ{sup −}) leads to enhanced sensitivity for dark matter masses above m{sub DM} ∼ 200 GeV.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2016

Can I solve my structure by SAD phasing? Planning an experiment, scaling data and evaluating the useful anomalous correlation and anomalous signal

A key challenge in the SAD phasing method is solving a structure when the anomalous signal-to-noise ratio is low. Here, we describe algorithms and tools for evaluating and optimizing the useful anomalous correlation and the anomalous signal in a SAD experiment. A simple theoretical framework [Terwilliger et al. (2016), Acta Cryst. D 72 , 346–358] is used to develop methods for planning a SAD experiment, scaling SAD data sets and estimating the useful anomalous correlation and anomalous signal in a SAD data set. The phenix.plan_sad_experiment tool uses a database of solved and unsolved SAD data sets and the expected characteristics of a SAD data set to estimate the probability that the anomalous substructure will be found in the SAD experiment and the expected map quality that would be obtained if the substructure were found. The phenix.scale_and_merge tool scales unmerged SAD data from one or more crystals using local scaling and optimizes the anomalous signal by identifying the systematic differences among data sets, and the phenix.anomalous_signal tool estimates the useful anomalous correlation and anomalous signal after collecting SAD data and estimates the probability that the data set can be solved and the likely figure of merit of phasing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Small-Signal Stability of Grid-Forming Inverters Using Current-Limiting and Frequency Stabilization

This paper presents a small-signal stability analysis of grid-forming (GFM) inverters under current-limiting conditions. It examines how adjustments in virtual impedance angles, implemented through advanced current-limiting and frequency stabilization techniques, influence small-signal stability. This paper studies a GFM inverter control integrating a fictitious power technique stabilizing primary control by adding a virtual power term and a hybrid current limiter integrating virtual impedance in the anti-wind-up feedback with current reference saturation limiting. A small-signal model is developed to assess the impact of virtual impedance angles on GFM inverter dynamics during grid disturbances, such as voltage drops. The findings indicate that although increasing the virtual impedance angle (to make it more inductive) enhances large-signal stability and voltage support during faults, it can induce oscillations and lead to instability if the angle exceeds certain thresholds. Based on the small-signal models, this paper provides design considerations for the current-limiter impedances to ensure reliable GFM inverter behavior under grid disturbances while maintaining small-signal stability.

current limiting↗
DOE OSTI2023

Network-Wide Traffic Signal Control Using Bilinear System Modeling and Adaptive Optimization

This study proposes a new multi-input multi-output optimal bilinear signal control method in which a bilinear dynamic model approximation is used to capture the nonlinear dynamics of the urban traffic networks. With signal green time splits as the control input and traffic delay changes as the output for each intersections in the network, a bilinear system model was developed, which, on the basis of linear system modeling, takes interactions among traffic delays and signal timing splits into consideration. Based on the bilinear system modeling framework, we conducted two steps in each time interval to derive traffic control strategies: (1) we used the normalized least-squared algorithm to estimate system parameters; and (2) we solved an online optimization problem to obtain the updated traffic control inputs for the signal timing that minimizes future traffic delays. We evaluated the proposed method in a microscopic traffic simulation environment (VISSIM) with a 35-intersection network of Bellevue city in Washington. Two different traffic demand patterns: (1) normal traffic demands; and (2) time-varying traffic demands were simulated to compare the performance of different control strategies. Experimental results show that (1) the proposed bilinear system model can better describe traffic system dynamics than linear-model based methods, such as our previously developed linear-quadratic regulator control; and (2) the proposed method outperforms the state-of-the-art signal control strategies, namely the max-pressure and the self-organizing traffic light control methods. We have also shown that the proposed method is applicable to all other possible network layouts and signal controller phasing structures.

42 ENGINEERING↗
DOE OSTI2019

21 cm Signal Recovery via Robust Principal Component Analysis

The redshifted 21 cm signal from neutral hydrogen (H i) is potentially a very powerful probe for cosmology, but a difficulty in its observation is that it is much weaker than foreground radiation from the Milky Way as well as extragalactic radio sources. The foreground radiation at different frequencies, however, is coherent along one line of sight, and various methods of foreground subtraction based on this property have been proposed. In this paper, we present a new method based on robust principal component analysis (RPCA) to subtract the foreground and extract the 21 cm signal, which explicitly uses both the low-rank property of the frequency covariance matrix (i.e., frequency coherence) of the foreground and the sparsity of the frequency covariance matrix of the 21 cm signal. The low-rank property of the foreground’s frequency covariance has been exploited in many previous works on foreground subtraction, but to our knowledge the sparsity of the frequency covariance of the 21 cm signal is first explored here. By exploiting both properties in the RPCA method, the frequency covariance matrix of the foreground and the 21 cm signal can be separated accurately. We then use the generalized internal linear combination method to recover the 21 cm signal from the data. Our method is applicable both to a small patch of sky with the flat-sky approximation and to a large area of sky where the sphericity has to be considered. It is also easy to extend to deal with more complex conditions such as a sky map with defects.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS2002

Root gravitropism: an experimental tool to investigate basic cellular and molecular processes underlying mechanosensing and signal transmission in plants

The ability of plant organs to use gravity as a guide for growth, named gravitropism, has been recognized for over two centuries. This growth response to the environment contributes significantly to the upward growth of shoots and the downward growth of roots commonly observed throughout the plant kingdom. Root gravitropism has received a great deal of attention because there is a physical separation between the primary site for gravity sensing, located in the root cap, and the site of differential growth response, located in the elongation zones (EZs). Hence, this system allows identification and characterization of different phases of gravitropism, including gravity perception, signal transduction, signal transmission, and curvature response. Recent studies support some aspects of an old model for gravity sensing, which postulates that root-cap columellar amyloplasts constitute the susceptors for gravity perception. Such studies have also allowed the identification of several molecules that appear to function as second messengers in gravity signal transduction and of potential signal transducers. Auxin has been implicated as a probable component of the signal that carries the gravitropic information between the gravity-sensing cap and the gravity-responding EZs. This has allowed the identification and characterization of important molecular processes underlying auxin transport and response in plants. New molecular models can be elaborated to explain how the gravity signal transduction pathway might regulate the polarity of auxin transport in roots. Further studies are required to test these models, as well as to study the molecular mechanisms underlying a poorly characterized phase of gravitropism that is independent of an auxin gradient.

Non-NASA Center↗
NASA NTRS1998

Calcium signals and calcium channels in osteoblastic cells

Calcium (Ca2+) channels are present in non-excitable as well as in excitable cells. In bone cells of the osteoblast lineage, Ca2+ channels play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. They are also proposed to modulate paracrine signaling between bone-forming osteoblasts and bone-resorbing osteoclasts at local sites of bone remodeling. Calcium signals are characterized by transient increases in intracellular Ca2+ levels that are associated with activation of intracellular signaling pathways that control cell behavior and phenotype, including patterns of gene expression. Development of Ca2+ signals is a tightly regulated cellular process that involves the concerted actions of plasma membrane and intracellular Ca2+ channels, along with Ca2+ pumps and exchangers. This review summarizes the current state of knowledge concerning the structure, function, and role of Ca2+ channels and Ca2+ signals in bone cells, focusing on the osteoblast.

Non-NASA Center↗
NASA NTRS2003

Modelling protein functional domains in signal transduction using Maude

Modelling of protein-protein interactions in signal transduction is receiving increased attention in computational biology. This paper describes recent research in the application of Maude, a symbolic language founded on rewriting logic, to the modelling of functional domains within signalling proteins. Protein functional domains (PFDs) are a critical focus of modern signal transduction research. In general, Maude models can simulate biological signalling networks and produce specific testable hypotheses at various levels of abstraction. Developing symbolic models of signalling proteins containing functional domains is important because of the potential to generate analyses of complex signalling networks based on structure-function relationships.

Signal Transduction↗
NASA NTRS2017

Osteogenic Transcription Regulated by Exaggerated Stretch Loading via Convergent Wnt Signaling

Cell and animal studies conducted onboard the International Space Station and formerly the Shuttle flights have provided data illuminating the deleterious biological response of bone to mechanical unloading. Down regulation of proliferative mechanisms within stem cell populations of the osteogenic niche is a suggested mechanism for loss of bone mass. However the intercellular communicative cues from osteoblasts and osteocytes in managing stem cell proliferation and osteogenic differentiation are largely unknown. In this investigation, MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells, are co-culture under dynamic tensile conditions and evaluated for phenotypic expression of biochemical signaling proteins influential in driving stem cell differentiation. MLO-Y4 and MC3T3-E1 were co-cultured on polyethersulfone membrane with a 0.45m porosity to permit soluble factor transfer and direct cell-cell gap junction signaling. Cyclic tensile stimulation was applied for 48 h at a frequency of 0.1Hz and strain of 0.1. Total Live cell counts indicate mechanical activation of MC3T3-E1s inhibits proliferation while MLO-Y4s increase in number. However, the percent of live MLO-Y4s within the population is low (46.3 total count, *p0.05, n4) suggesting a potential apoptotic signaling cascade. Immunofluorescence demonstrated that stimulation of co-cultures elicits increased gap junction communication. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggest that an osteocyte-osteoblast signaling feedback mechanism may regulate mechanotransduction of an apoptotic cascade within osteocytes and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

mechanical stimulation↗
NASA NTRSDate not supplied

Navigation Doppler Lidar Signal Processing Architecture and Algorithms

A coherent Doppler lidar has been developed to address the need for a high-performance, compact, and cost-effective velocity and altitude sensor onboard landing vehicles. One of the core subsystems within NDL is its signal processing architecture. The primary function of this subsystem is to digitize the analog output of the homodyned signal received from the photo-diode associated with each telescope, process this signal in the frequency domain, and then turn this information into velocity and range measurements. A secondary function of this subsystem is to setup and control the internal components within NDL and to enable the instrument to interface with external systems by receiving commands, sending telemetry, and synchronizing its measurements with external clocks and pulses. This paper will give an overview of the signal processing architecture within NDL. This will include a discussion on its fundamental processing components and the core signal processing algorithms. Command, telemetry and internal component controls will also be discussed as will how the signal processing architecture has also evolved over the years of development. We will discuss provisions for robust operation including Triple-Mode Redundancy (TMR) within NDL’s Field Programmable Gate Array (FPGA) and storage elements, a fault-tolerant boot process, and Error Detection and Correction (EDAC) on the Static Random-Access Memories (SRAMs). Finally, we conclude this paper with how this architecture could continue to evolve.

Doppler Lidar↗
NASA NTRSDate not supplied

The Design of a Flexible, Interoperable Navigation Signal for Future Lunar Missions

The LunaNet Interoperability Specification (LNIS) is a set of standards currently under development by NASA, ESA, and JAXA, which define a common, interoperable set of services and interfaces for lunar communication and navigation. The LNIS includes specifications for the GNSS-like Augmented Forward Signal (AFS). The LANS (Lunar Augmented Navigation Service) will be comprised of Multiple LunaNet Service Provider (LNSP) nodes broadcasting the AFS, such as NASA’s LCRNS (Lunar Communications Relay and Navigation Systems), ESA’s Moonlight LCNS (Lunar Communication and Navigation Services) and the Japan LNSS (Lunar Navigation Satellite System). The LANS will provide a GNSS-like capability enabling orbiting and surface users in lunar space (such as Artemis) to estimate their position, velocity and time as described in Giordano et al., (2023). Initial capabilities will focus on providing service to the lunar South pole region. The specification of AFS defines two orthogonal signal components on a single carrier, with the in-phase component (AFS-I) being a lower-chip-rate data channel tailored for applications where low SWaP is critical (e.g., IoT devices or search and rescue), and the quadrature component (AFS-Q) being a high-chip-rate data-less pilot signal for high-precision, robust lunar navigation and positioning applications. An initial description of AFS was provided in the LNIS, (2023), and initial analysis results were shown in Dafesh, et al., (2024). In this work, we provide rationale for updates to the LNIS that define key aspects of the signal including the primary spreading code designs for the data and pilot channels, and a three-tiered overlay code approach for the pilot channel that provides flexible signal acquisition alternatives, rapid time dissemination and robust frame Sync. The paper also describes a robust data sync word that is designed to enable frame Sync. for low-SWaP receivers that only use the I channel, as well as a low-density parity check code (LDPC) data message encoding design and interleaving definition. The work further describes the impact of the updated AFS design in terms of improved acquisition performance, interference resistance, navigation message capabilities and rapid absolute time dissemination for users able to access clock and ephemeris data over an external network. The cross-correlation and synchronization performance of the AFS design is also compared to potential alternatives, further providing rationale for the final signal design configuration.

LANS↗
NASA NTRS2025

The Design of a Flexible, Interoperable Navigation Signal for Future Lunar Missions

The LunaNet Interoperability Specification (LNIS) is a set of standards currently under development by NASA, ESA, and JAXA, which define a common, interoperable set of services and interfaces for lunar communication and navigation. The LNIS includes specifications for the GNSS-like Augmented Forward Signal (AFS). The LANS (Lunar Augmented Navigation Service) will be comprised of Multiple LunaNet Service Provider (LNSP) nodes broadcasting the AFS, such as NASA’s LCRNS (Lunar Communications Relay and Navigation Systems), ESA’s Moonlight LCNS (Lunar Communication and Navigation Services) and the Japan LNSS (Lunar Navigation Satellite System). The LANS will provide a GNSS-like capability enabling orbiting and surface users in lunar space (such as Artemis) to estimate their position, velocity and time as described in Giordano et al., (2023). Initial capabilities will focus on providing service to the lunar South pole region. The specification of AFS defines two orthogonal signal components on a single carrier, with the in-phase component (AFS-I) being a lower-chip-rate data channel tailored for applications where low SWaP is critical (e.g., IoT devices or search and rescue), and the quadrature component (AFS-Q) being a high-chip-rate data-less pilot signal for high-precision, robust lunar navigation and positioning applications. An initial description of AFS was provided in the LNIS, (2023), and initial analysis results were shown in Dafesh, et al., (2024). In this work, we provide rationale for updates to the LNIS that define key aspects of the signal including the primary spreading code designs for the data and pilot channels, and a three-tiered overlay code approach for the pilot channel that provides flexible signal acquisition alternatives, rapid time dissemination and robust frame Sync. The paper also describes a robust data sync word that is designed to enable frame Sync. for low-SWaP receivers that only use the I channel, as well as a low-density parity check code (LDPC) data message encoding design and interleaving definition. The work further describes the impact of the updated AFS design in terms of improved acquisition performance, interference resistance, navigation message capabilities and rapid absolute time dissemination for users able to access clock and ephemeris data over an external network. The cross-correlation and synchronization performance of the AFS design is also compared to potential alternatives, further providing rationale for the final signal design configuration.

LunaNet↗
DOE OSTI2015

In-Containment Signal Acquisition and Data Transmission via Power Lines within High Dose Areas of Nuclear Power Plants

Signal acquisition and data transmission for innovative sensor systems and networks inside the containment of nuclear power plants (NPPs) is still a challenge with respect to safety, performance, reliability, availability, and costs. This especially applies to equipment upgrades for existing plants, special measurements, but also for new builds. This paper presents a novel method for efficient and cost-effective sensor signal acquisition and data transmission via power lines, in order to cope with the disadvantages of common system architectures that often suffer from poor signal integrity due to raw data transmissions via long cables, huge efforts and costs for installation, and low flexibility with respect to maintenance and upgrades. A transmitter-receiver architecture is proposed that allows multiplexing of multiple sensor inputs for unidirectional point-to-point transmission by superimposing information signals on existing AC or DC supply lines, but also on active and inactive sensor wires, or spare cables, using power line communication (PLC) technology. Based on commercial off-the-shelf (COTS) electronic parts, a radiation hard transmitter hardware is designed to operate in harsh environment within the containment during full plant operation. The system's modular approach allows application specific trade-offs between redundancy and throughput regarding data transmission, as well as various sensor input front-ends which are compatible with state of the art systems. PLC technology eliminates the need for costly installation of additional cables and wall penetrations, while providing a complementary and diverse communication technology for upgrades of existing systems. At the receiver side in low dose areas, signals are extracted from the power line, demodulated, and de-multiplexed, in order to regain the original sensor signal information and provide it either in analog or digital output format. Successful laboratory qualification tests, field trails, and a demonstrator setup installation within a NPP verify the overall performance of the proposed system. (authors)

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2017

Development of a transient signal validation technique via a modified kernel regression model - 365

The demand for robust and resilient performance has led to the use of online-monitoring and signal validation techniques to monitor the process parameters and equipment conditions using several empirical models. One of these models is kernel regression (KR). Although KR is being used and performed excellently when applied to steady state, it has limitation in time-varying data that has several repetition of the same data point of the signals, especially if those signals are used to infer the other signals. In addition, many situations are related to variation and fluctuation during normal states, such as transient - start-up and shutdown mode. However, accurate estimation of the process signal can lead to the proper understanding of the equipment behaviours as well as enhance the online monitoring applications. In the sight of foregoing, this paper proposed a modified KR model, especially for transient signal validation to resolve the setback of conventional KR by improving the measure of similarities in the conventional KR. The performance of the proposed model is verified using both experimental data and the plant simulation data, and its results are compared with that of conventional KR. The results show that the proposed model has a greater robustness in particular situations compared to conventional KR, and it can be used to improve process and equipment monitoring applications. (authors)

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2018

Role of the signal sequence in proteorhodopsin biogenesis in E. coli

Blue-absorbing proteorhodopsin (BPR) from marine bacteria is a retinal-bound, light-activated, outwards proton transporter containing seven α-helical transmembrane segments (TMS). It is synthesized as a precursor species (pre-BPR) with a predicted N-terminal signal sequence that is cleaved to yield the mature protein. While optimizing the production of BPR in Escherichia coli to facilitate the construction of bioprotonic devices, we observed significant pre-BPR accumulation in the inner membrane and explored signal sequence requirements and export pathway. Here, we report that BPR does not rely on the Sec pathway for inner membrane integration, and that although it greatly enhances yields, its signal sequence is not necessary to obtain a functional product. We further show that an unprocessable version of pre-BPR obtained by mutagenesis of the signal peptidase I site exhibits all functional attributes of the wild-type protein and has the advantage of being produced at higher levels. Our results are consistent with the BPR signal sequence being recognized by the signal recognition particle (SRP; a protein that orchestrates the cotranslational biogenesis of inner membrane proteins) and serving as a beneficial “pro” domain rather than a traditional secretory peptide.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Vascular endothelial growth factor signaling regulates the segregation of artery and vein via ERK activity during vascular development

Highlights: ► VEGF-A signaling regulates the segregation of axial vessels. ► VEGF-A signaling is mediated by PKC and ERK in this process. ► Ectopic activation of ERK is sufficient to rescue defects in vessel segregation. -- Abstract: Segregation of two axial vessels, the dorsal aorta and caudal vein, is one of the earliest patterning events occur during development of vasculature. Despite the importance of this process and recent advances in our understanding on vascular patterning during development, molecular mechanisms that coordinate the segregation of axial vessels remain largely elusive. In this report, we find that vascular endothelial growth factor-A (Vegf-A) signaling regulates the segregation of dorsal aorta and axial vein during development. Inhibition of Vegf-A pathway components including ligand Vegf-A and its cognate receptor Kdrl, caused failure in segregation of axial vessels in zebrafish embryos. Similarly, chemical inhibition of Mitogen-activated protein kinase kinase (Map2k1)/Extracellular-signal-regulated kinases (Erk) and phosphatidylinositol 3-kinases (PI3 K), which are downstream effectors of Vegf-A signaling pathway, led to the fusion of two axial vessels. Moreover, we find that restoring Erk activity by over-expression of constitutively active MEK in embryos with a reduced level of Vegf-A signaling can rescue the defects in axial vessel segregation. Taken together, our data show that segregation of axial vessels requires the function of Vegf-A signaling, and Erk may function as the major downstream effector in this process.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

NHERF-1 regulation of EGF and neurotensin signalling in HT-29 epithelial cells

Highlights: ► NHERF-1 expression was abundant throughout HT-29 cells consistent with a cancerous phenotype. ► Knockdown of NHERF-1 lead to a significant reduction in cell proliferation. ► EGF and neurotensin-mediated proliferation was inhibited by knockdown of NHERF-1. ► Neurotensin-mediated Ca{sup 2+} response was abolished by knockdown of NHERF-1. -- Abstract: Neurotensin receptors (NT-R) and the epidermal growth factor receptors (EGF-R) are commonly overexpressed in many epithelial origin tumours. In addition to their role as mitogenic mediators through specific cell signalling, recent studies indicate that the activity/expression of scaffold proteins responsible for the assembly and coordination of the signalling complexes may also have central roles in epithelial transformation. In particular, the “epithelial” PSD-95/Dlg/Zo-1 (PDZ) scaffold/adapter protein, Na{sup +}/H{sup +} exchanger regulatory factor isoform one (NHERF-1), has been identified as a potential regulator of cellular transformation. NHERF-1 is a known regulator of EGF-R function and plays numerous roles in G-protein-coupled receptor signalling. Because of the synergistic signalling between these two potent mitogens, we investigated a potential role for NHERF-1 in the molecular mechanism linking the aberrant proliferative phenotype initiated by some G-Protein-coupled receptor activators in the colon adenocarcinoma HT-29 cell line. Knockdown (80%) of endogenous NHERF-1 leads to significant reduction in proliferation rate; an effect that could not be recovered by exogenous application of either NT or EGF. Inhibition of the EGF-R with AG1487 also inhibited proliferation and this effect could not be recovered with NT. Knockdown of NHERF-1 significantly altered the expression of the EGF-R, and almost completely abolished the NT-mediated increases in intracellular free Ca{sup 2+}. Knockdown of NHERF-1 also attenuated UTP-mediated purinergic Ca{sup 2+} signalling. Taken together, these data suggest that NHERF-1 plays a more central role in cell proliferation by modulating Gq-mediated signalling pathways.

60 APPLIED LIFE SCIENCES↗