Proteasomes regulate the duration of erythropoietin receptor activation by controlling down-regulation of cell surface receptors

2000 ◽  
Vol 28 (5) ◽  
pp. A284-A284
Author(s):  
F. Verdier ◽  
P. Walrafen ◽  
N. Hubert ◽  
S. Chretien ◽  
S. Gisselbrecht ◽  
...  
Keyword(s):  
Cell Surface ◽  
Receptor Activation ◽  
Erythropoietin Receptor ◽  
Cell Surface Receptors ◽  
Down Regulation ◽  
Surface Receptors

scholarly journals Proteasomes Regulate the Duration of Erythropoietin Receptor Activation by Controlling Down-regulation of Cell Surface Receptors

2000 ◽  
Vol 275 (24) ◽  
pp. 18375-18381 ◽  
Author(s):  
Frédérique Verdier ◽  
Pierre Walrafen ◽  
Nathalie Hubert ◽  
Stany Chrétien ◽  
Sylvie Gisselbrecht ◽  
...  
Keyword(s):  
Cell Surface ◽  
Receptor Activation ◽  
Erythropoietin Receptor ◽  
Cell Surface Receptors ◽  
Down Regulation ◽  
Surface Receptors

scholarly journals Vav Family Proteins Couple to Diverse Cell Surface Receptors

2000 ◽  
Vol 20 (17) ◽  
pp. 6364-6373 ◽  
Author(s):  
Sheri L. Moores ◽  
Laura M. Selfors ◽  
Jessica Fredericks ◽  
Timo Breit ◽  
Keiko Fujikawa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
Nucleotide Exchange ◽  
Surface Receptors ◽  
Downstream Signaling

ABSTRACT Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple with similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation. Integrin-induced tyrosine phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT-dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NFκB-dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways.

RECEPTOR-DEPENDENT SENSITIVITY OF NF-κB TO LOW PHYSIOLOGICAL LEVEL

2013 ◽  
Vol 21 (03) ◽  
pp. 1350018
Author(s):  
PANPAN YANG ◽  
TIANSHOU ZHOU
Keyword(s):  
Cell Surface ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
High Dose ◽  
Physiological Level ◽  
Information Encoding ◽  
Surface Receptors ◽  
Receptor Number ◽  
Activation Rates

In the NFκB signaling pathway, cells respond to different concentrations of the TNFα signal by means of NFκB transcription factors. Previous studies showed that most cells are activated under high-dose stimulations and NFκB activation results in oscillations in nuclear NFκB abundance. Here, by analyzing sensitivity gain for the response of the nuclear NFκB to the number of cell-surface receptors under low-dose stimulations, we show that changes in the receptor number can give rise to significant changes in the nonsaturation part of the dose–response curve, where the receptor activation rates are very sensitive to stimulations. In addition, the number of the activated receptors tends to increase in a large range of stimulation dose and can significantly influence the expression of the downstream genes. These results imply that the number of cell-surface receptors plays a role of information encoding like frequency or amplitude encoding described in previous studies.

Receptor clustering and activation by multivalent interaction through recognition peptides presented on exosomes

2017 ◽  
Vol 53 (2) ◽  
pp. 317-320 ◽  
Author(s):  
I. Nakase ◽  
N. Ueno ◽  
M. Katayama ◽  
K. Noguchi ◽  
T. Takatani-Nakase ◽  
...  
Keyword(s):  
Cell Surface ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
Receptor Clustering ◽  
Surface Receptors ◽  
Peptide Segments

A system for inducing clustering of cell surface receptors via recognition peptide segments displayed on exosomes, leading to receptor activation.

scholarly journals The Na+/H+ Exchanger Regulatory Factor Stabilizes Epidermal Growth Factor Receptors at the Cell Surface

2004 ◽  
Vol 15 (12) ◽  
pp. 5470-5480 ◽  
Author(s):  
Cheri S. Lazar ◽  
Catherine M. Cresson ◽  
Douglas A. Lauffenburger ◽  
Gordon N. Gill
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptors ◽  
Cell Surface Receptors ◽  
Epidermal Growth Factor Receptors ◽  
Regulatory Factor ◽  
Down Regulation ◽  
Surface Receptors ◽  
Epidermal Growth

Ligand binding to cell surface receptors initiates both signal transduction and endocytosis. Although signaling may continue within the endocytic compartment, down-regulation is the major mechanism that controls the concentration of cell surface receptors, their ability to receive environmental signals, and the ultimate strength of biological signaling. Internalization, recycling, and trafficking of receptor tyrosine kinases (RTKs) within the endosome compartment are each regulated to control the overall process of down-regulation. We have identified the Na+/H+ exchanger regulatory factor (NHERF) as an important molecular component that stabilizes epidermal growth factor receptors (EGFRs) at the cell surface to restrict receptor down-regulation. The NH2-terminal PDZ domain (PDZ 1) of NHERF specifically binds to an internal peptide motif located within the COOH-terminal regulatory domain of EGFR. Expression of NHERF slows the rate of EGF-induced receptor degradation. A point mutation that abolishes the PDZ 1 recognition sequence of EGFR enhances the rate of ligand-induced endocytosis and down-regulation of EGFR. Similarly, expression of a dominant negative mutant of NHERF enhances EGF-induced receptor down-regulation. In contrast to β-adrenergic receptors where NHERF enhances recycling of internalized receptors, NHERF stabilizes EGFR at the cell surface and slows the rate of endocytosis without affecting recycling. Although the mechanisms differ, for both RTKs and G protein-coupled receptors, the overall effect of NHERF is to enhance the fraction of receptors present at the cell surface.

Interactions of VEGF isoforms with VEGFR-1, VEGFR-2, and neuropilin in vivo: a computational model of human skeletal muscle

2007 ◽  
Vol 292 (1) ◽  
pp. H459-H474 ◽  
Author(s):  
Feilim Mac Gabhann ◽  
Aleksander S. Popel
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Cell Surface ◽  
Computational Model ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
Vastus Lateralis Muscle ◽  
Surface Receptors ◽  
Vegf Isoforms

The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF121, VEGF165), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The model is general and could be applied to any tissue; here we apply the model to simulate the transport of VEGF isoforms in human vastus lateralis muscle, which is extensively studied in physiological experiments. The simulations predict the distribution of VEGF isoforms in resting (nonexercising) muscle and the activation of VEGFR signaling. Little of the VEGF protein in muscle is present as free, unbound extracellular cytokine; the majority is bound to the cell surface receptors or to the extracellular matrix. However, interstitial sequestration of VEGF165 does not affect steady-state receptor binding. In the absence of neuropilin, VEGF121 and VEGF165 behave similarly, but neuropilin enhances the binding of VEGF165 to VEGFR-2. This model is the first to study VEGF tissue distribution and receptor activation in human muscle, and it provides a platform for the design and evaluation of therapeutic approaches.

scholarly journals Adenovirus RIDβ Subunit Contains a Tyrosine Residue That Is Critical for RID-Mediated Receptor Internalization and Inhibition of Fas- and TRAIL-Induced Apoptosis

2002 ◽  
Vol 76 (22) ◽  
pp. 11329-11342 ◽  
Author(s):  
Drew L. Lichtenstein ◽  
Peter Krajcsi ◽  
David J. Esteban ◽  
Ann E. Tollefson ◽  
William S. M. Wold
Keyword(s):  
Cell Surface ◽  
Death Receptor ◽  
Receptor Internalization ◽  
Cell Surface Receptors ◽  
Trail Receptor ◽  
Tyrosine Residue ◽  
Down Regulation ◽  
Surface Receptors ◽  
Sorting Signal ◽  
Induced Apoptosis

ABSTRACT The adenovirus-encoded receptor internalization and degradation (RID) protein (previously named E3-10.4K/14.5K), which is composed of RIDα and RIDβ subunits, down-regulates a number of cell surface receptors in the tumor necrosis factor (TNF) receptor superfamily, namely Fas, TRAIL receptor 1, and TRAIL receptor 2. Down-regulation of these “death” receptors protects adenovirus-infected cells from apoptosis induced by the death receptor ligands Fas ligand and TRAIL. RID also down-regulates certain tyrosine kinase cell surface receptors, especially the epidermal growth factor receptor (EGFR). RID-mediated Fas and EGFR down-regulation occurs via endocytosis of the receptors into endosomes followed by transport to and degradation within lysosomes. However, the molecular interactions underlying this function of RID are unknown. To investigate the molecular determinants of RIDβ that are involved in receptor down-regulation, mutations within the cytoplasmic tail of RIDβ were constructed and the mutant proteins were analyzed for their capacity to internalize and degrade Fas and EGFR and to protect cells from death receptor ligand-induced apoptosis. The results demonstrated the critical nature of a tyrosine residue near the RIDβ C terminus; mutation of this residue to alanine abolished RID function. Mutating the tyrosine to phenylalanine did not abolish the function of RID, arguing that phosphorylation of the tyrosine is not required for function. These data suggest that this tyrosine residue forms part of a tyrosine-based sorting signal (Yxxφ). Additional mutations that target another potential sorting motif and several possible protein-protein interaction motifs had no discernible effect on RID function. It was also demonstrated that mutation of serine 116 to alanine eliminated phosphorylation of RIDβ but did not affect any of the functions of RID that were examined. These results suggest a model in which the tyrosine-based sorting signal in RID plays a role in RID's ability to down-regulate receptors.

scholarly journals Cell Surface Receptors: Rapid Quantification of Live Cell Receptors Using Bioluminescence in a Flow-Based Microfluidic Device (Small 8/2015)

Small ◽  
2015 ◽  
Vol 11 (8) ◽  
pp. 1012-1012
Author(s):  
Ramesh Ramji ◽  
Cheong Fook Cheong ◽  
Hiroaki Hirata ◽  
Abdur Rub Abdur Rahman ◽  
Chwee Teck Lim
Keyword(s):  
Cell Surface ◽  
Microfluidic Device ◽  
Live Cell ◽  
Cell Surface Receptors ◽  
Cell Receptors ◽  
Surface Receptors ◽  
Rapid Quantification
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