scholarly journals Chemical integration of proteins in signaling and development

2015 ◽  
Author(s):  
Jeffrey M. Dick
Keyword(s):  
Signal Transduction ◽  
Sonic Hedgehog ◽  
Molecular Mechanisms ◽  
Protein Translation ◽  
Cell Surface Receptor ◽  
Metastable Equilibrium ◽  
Second Stage ◽  
Gli Proteins ◽  
Surface Receptor ◽  
High Level

In developing embryos of eukaryotes, varying concentrations and/or duration of exposure to morphogens induce and repress transcription factors (TFs) in a regular order, thereby acting as signals for cell differentiation. I present a chemical thermodynamic model for the formation and degradation of the morphogen Sonic hedgehog (Shh) and the major TFs involved in dorsal-ventral patterning of the vertebrate neural tube. This two-stage model first considers introduction of Shh into a chemically defined (oxidizing) environment. As the system is driven away from metastable equilibrium, the TFs progressively become more stable than Shh, as indicated by comparison of the calculated overall energies of formation (chemical affinity). In the second stage, a gradual return to metastable equilibrium with Shh drives transitions in the relative stabilities of the TFs that follow the experimental patterns of TF expression. At the intracellular level, the major proteins in the signal transduction network show a metastability progression among reactions of Shh and its cell-surface receptor and the intracellular Gli proteins that act as activators and repressors of transcription. If the endocytosis and degradation of receptor-ligand complexes are coupled to localized protein translation, the consequent thermodynamic constraints may represent a high-level source of specificity that coexists with molecular mechanisms of signal transduction.

scholarly journals Brassinosteroid signal transduction from cell-surface receptor kinases to nuclear transcription factors

2009 ◽  
Vol 11 (10) ◽  
pp. 1254-1260 ◽  
Author(s):  
Tae-Wuk Kim ◽  
Shenheng Guan ◽  
Yu Sun ◽  
Zhiping Deng ◽  
Wenqiang Tang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Cell Surface ◽  
Cell Surface Receptor ◽  
Receptor Kinases ◽  
Surface Receptor

scholarly journals Thyroid Hormone and P-Glycoprotein in Tumor Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Paul J. Davis ◽  
Sandra Incerpi ◽  
Hung-Yun Lin ◽  
Heng-Yuan Tang ◽  
Thangirala Sudha ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Cell Surface Receptor ◽  
P Glycoprotein ◽  
Surface Receptor

P-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1) is a plasma membrane efflux pump that when activated in cancer cells exports chemotherapeutic agents. Transcription of the P-gp gene (MDR1) and activity of the P-gp protein are known to be affected by thyroid hormone. A cell surface receptor for thyroid hormone on integrinαvβ3 also binds tetraiodothyroacetic acid (tetrac), a derivative of L-thyroxine (T4) that blocks nongenomic actions of T4and of 3,5,3′-triiodo-L-thyronine (T3) atαvβ3. Covalently bound to a nanoparticle, tetrac as nanotetrac acts at the integrin to increase intracellular residence time of chemotherapeutic agents such as doxorubicin and etoposide that are substrates of P-gp. This action chemosensitizes cancer cells. In this review, we examine possible molecular mechanisms for the inhibitory effect of nanotetrac on P-gp activity. Mechanisms for consideration include cancer cell acidification via action of tetrac/nanotetrac on the Na+/H+exchanger (NHE1) and hormone analogue effects on calmodulin-dependent processes and on interactions of P-gp with epidermal growth factor (EGF) and osteopontin (OPN), apparently viaαvβ3. Intracellular acidification and decreased H+efflux induced by tetrac/nanotetrac via NHE1 is the most attractive explanation for the actions on P-gp and consequent increase in cancer cell retention of chemotherapeutic agent-ligands of MDR1 protein.

scholarly journals Molecular Mechanisms of Brassinosteroid-Mediated Responses to Changing Environments in Arabidopsis

2020 ◽  
Vol 21 (8) ◽  
pp. 2737 ◽  
Author(s):  
Minghui Lv ◽  
Jia Li
Keyword(s):  
Molecular Mechanisms ◽  
Cell Surface Receptor ◽  
Signal Molecules ◽  
Environmental Cues ◽  
Receptor Complex ◽  
Changing Environments ◽  
Plant Adaptations ◽  
Surface Receptor ◽  
Growth Promoting ◽  
External Stimuli

Plant adaptations to changing environments rely on integrating external stimuli into internal responses. Brassinosteroids (BRs), a group of growth-promoting phytohormones, have been reported to act as signal molecules mediating these processes. BRs are perceived by cell surface receptor complex including receptor BRI1 and coreceptor BAK1, which subsequently triggers a signaling cascade that leads to inhibition of BIN2 and activation of BES1/BZR1 transcription factors. BES1/BZR1 can directly regulate the expression of thousands of downstream responsive genes. Recent studies in the model plant Arabidopsis demonstrated that BR biosynthesis and signal transduction, especially the regulatory components BIN2 and BES1/BZR1, are finely tuned by various environmental cues. Here, we summarize these research updates and give a comprehensive review of how BR biosynthesis and signaling are modulated by changing environments and how these changes regulate plant adaptive growth or stress tolerance.

scholarly journals Constitutive Activation and Inactivation of Mutations Inducing Cell Surface Loss of Receptor and Impairing of Signal Transduction of Agonist-Stimulated Eel Follicle-Stimulating Hormone Receptor

2020 ◽  
Vol 21 (19) ◽  
pp. 7075
Author(s):  
Munkhzaya Byambaragchaa ◽  
Jeong-Soo Kim ◽  
Hong-Kyu Park ◽  
Dae-Jung Kim ◽  
Sun-Mee Hong ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Hormone Receptor ◽  
Follicle Stimulating Hormone ◽  
Chinese Hamster ◽  
Cell Surface Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Surface Receptor ◽  
Stimulating Hormone

In the present study, we investigated the signal transduction of mutants of the eel follicle-stimulating hormone receptor (eelFSHR). Specifically, we examined the constitutively activating mutant D540G in the third intracellular loop, and four inactivating mutants (A193V, N195I, R546C, and A548V). To directly assess functional effects, we conducted site-directed mutagenesis to generate mutant receptors. We measured cyclic adenosine monophosphate (cAMP) accumulation via homogeneous time-resolved fluorescence assays in Chinese hamster ovary (CHO-K1) cells and investigated cell surface receptor loss using an enzyme-linked immunosorbent assay in human embryonic kidney (HEK) 293 cells. The cells expressing eelFSHR-D540G exhibited a 23-fold increase in the basal cAMP response without agonist treatment. The cells expressing A193V, N195I, and A548V mutants had completely impaired signal transduction, whereas those expressing the R546C mutant exhibited little increase in cAMP responsiveness and a small increase in signal transduction. Cell surface receptor loss in the cells expressing inactivating mutants A193V, R546C, and A548V was clearly slower than in the cell expressing the wild-type eelFSHR. However, cell surface receptor loss in the cells expressing inactivating mutant N195I decreased in a similar manner to that of the cells expressing the wild-type eelFSHR or the activating mutant D540G, despite the completely impaired cAMP response. These results provide important information regarding the structure–function relationships of G protein-coupled receptors during signal transduction.

Regulation of c-ret expression by retinoic acid in rat metanephros: implication in nephron mass control

1998 ◽  
Vol 275 (6) ◽  
pp. F938-F945 ◽  
Author(s):  
Evelyne Moreau ◽  
José Vilar ◽  
Martine Lelièvre-Pégorier ◽  
Claudie Merlet-Bénichou ◽  
Thierry Gilbert
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Mrna Level ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
All Trans Retinoic Acid ◽  
Surface Receptor ◽  
Dose Dependent

Vitamin A and its derivatives have been shown to promote kidney development in vitro in a dose-dependent fashion. To address the molecular mechanisms by which all- trans-retinoic acid (RA) may regulate the nephron mass, rat kidneys were removed on embryonic day 14( E14) and grown in organ culture under standard or RA-stimulated conditions. By using RT-PCR, we studied the expression of the glial cell line-derived neurotrophic factor (GDNF), its cell surface receptor-α (GDNFR-α), and the receptor tyrosine kinase c-ret, known to play a major role in renal organogenesis. Expression of GDNF and GDNFR-α transcripts was high at the time of explantation and remained unaffected in culture with or without RA. In contrast, c-ret mRNA level, which was low in E14 metanephros and dropped rapidly in vitro, was increased by RA in a dose-dependent manner. The same is true at the protein level. Exogenous GDNF barely promotes additional nephron formation in vitro. Thus the present data establish c-ret as a key target of retinoids during kidney organogenesis.

scholarly journals Crystallization and preliminary X-ray diffraction analysis of the periplasmic domain of theEscherichia coliaspartate receptor Tar and its complex with aspartate

2014 ◽  
Vol 70 (9) ◽  
pp. 1219-1223 ◽  
Author(s):  
Takeshi Mise ◽  
Hideyuki Matsunami ◽  
Fadel A. Samatey ◽  
Ichiro N. Maruyama
Keyword(s):  
Escherichia Coli ◽  
Sodium Chloride ◽  
Molecular Mechanisms ◽  
Bacterial Chemotaxis ◽  
Cell Surface Receptor ◽  
X Ray Diffraction ◽  
X Ray ◽  
Space Groups ◽  
Surface Receptor ◽  
Periplasmic Domain

The cell-surface receptor Tar mediates bacterial chemotaxis toward an attractant, aspartate (Asp), and away from a repellent, Ni2+. To understand the molecular mechanisms underlying the induction of Tar activity by its ligands, theEscherichia coliTar periplasmic domain with and without bound aspartate (Asp-Tar and apo-Tar, respectively) were each crystallized in two different forms. Using ammonium sulfate as a precipitant, crystals of apo-Tar1 and Asp-Tar1 were grown and diffracted to resolutions of 2.10 and 2.40 Å, respectively. Alternatively, using sodium chloride as a precipitant, crystals of apo-Tar2 and Asp-Tar2 were grown and diffracted to resolutions of 1.95 and 1.58 Å, respectively. Crystals of apo-Tar1 and Asp-Tar1 adopted space groupP41212, while those of apo-Tar2 and Asp-Tar2 adopted space groupsP212121andC2, respectively.

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