scholarly journals Towards pharmacological intervention in inositol pyrophosphate signalling

2016 ◽  
Vol 44 (1) ◽  
pp. 191-196 ◽  
Author(s):  
Stephen B. Shears
Keyword(s):  
Molecular Basis ◽  
Cell Signalling ◽  
Cellular Protein ◽  
Pharmacological Intervention ◽  
Biological Functions ◽  
Future Directions ◽  
Inositol Pyrophosphate ◽  
Signalling Molecules ◽  
Intracellular Signals ◽  
Inositol Pyrophosphates

To help define the molecular basis of cellular signalling cascades, and their biological functions, there is considerable value in utilizing a high-quality chemical ‘probe’ that has a well-defined interaction with a specific cellular protein. Such reagents include inhibitors of protein kinases and small molecule kinases, as well as mimics or antagonists of intracellular signals. The purpose of this review is to consider recent progress and promising future directions for the development of novel molecules that can interrogate and manipulate the cellular actions of inositol pyrophosphates (PP-IPs)–a specialized, ‘energetic’ group of cell-signalling molecules in which multiple phosphate and diphosphate groups are crammed around a cyclohexane polyol scaffold.

Signalling during epidermal development

2007 ◽  
Vol 35 (1) ◽  
pp. 156-160 ◽  
Author(s):  
G.C. Ingram
Keyword(s):  
Cell Signalling ◽  
Cell Types ◽  
Cellular Level ◽  
In Planta ◽  
Future Directions ◽  
Signalling Molecules ◽  
Physical Accessibility ◽  
Epidermal Development ◽  
Cell Cell

The process of L1 specification early in plant embryogenesis, and subsequent maintenance and elaboration of epidermal organization, are fundamental to plant growth and fitness. To occur in a co-ordinated fashion, these processes require considerable cell–cell cross-talk. It is perhaps then unsurprising that several classes of plant RLKs (receptor-like kinases), as well as other membrane-localized signalling components, have been implicated both in epidermal specification and in patterning events governing the distribution of epidermal cell types. However, despite our growing knowledge of the roles of these signalling molecules, remarkably little is understood regarding their function at the cellular level. In particular the potential role of regulated proteolytic cleavage in controlling the activity of signalling molecules at the plant plasma membrane has remained largely unaddressed despite its massive importance in signalling in animal systems. Because of the relative physical accessibility of their expression domains, molecules involved in epidermal development present opportunities for investigating mechanisms of cell–cell signalling in planta. Advances in understanding the potential regulatory processing of membrane-localized signalling molecules during epidermal development will be examined using parallels with animal systems to highlight potential future directions for this field of research.

scholarly journals Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain

2011 ◽  
Vol 434 (3) ◽  
pp. 415-426 ◽  
Author(s):  
Nikhil A. Gokhale ◽  
Angelika Zaremba ◽  
Stephen B. Shears
Keyword(s):  
Mammalian Cells ◽  
Consensus Sequence ◽  
Lipid Vesicles ◽  
Lipid Binding ◽  
Binding Domain ◽  
Site Directed Mutagenesis ◽  
Inositol Pyrophosphate ◽  
Signalling Molecules ◽  
Catalytically Active ◽  
Inositol Pyrophosphates

The inositol pyrophosphates are multifunctional signalling molecules. One of the families of enzymes that synthesize the inositol pyrophosphates are the Vip1/PPIP5Ks (PP-InsP5 kinases). The kinase domains in Vip1/PPIP5Ks have been mapped to their N-terminus. Each of these proteins also possess a phosphatase-like domain of unknown significance. In the present study, we show that this phosphatase-like domain is not catalytically active. Instead, by using SPR (surface plasmon resonance) to study protein binding to immobilized lipid vesicles, we show that this domain is specialized for binding PtdIns(3,4,5)P3 (PPIP5K1 Kd=96 nM; PPIP5K2 Kd=705 nM). Both PtdIns(3,4)P2 and PtdIns(4,5)P2 are significantly weaker ligands, and no significant binding of PtdIns(3,5)P2 was detected. We confirm the functional importance of this domain in inositol lipid binding by site-directed mutagenesis. We present evidence that the PtdIns(3,4,5)P3-binding domain is an unusual hybrid, in which a partial PH (pleckstrin homology) consensus sequence is spliced into the phosphatase-like domain. Agonist-dependent activation of the PtdIns 3-kinase pathway in NIH 3T3 cells drives translocation of PPIP5K1 from the cytosol to the plasma membrane. We have therefore demonstrated receptor-regulated compartmentalization of inositol pyrophosphate synthesis in mammalian cells.

Caveolin-1, galectin-3 and lipid raft domains in cancer cell signalling

2015 ◽  
Vol 57 ◽  
pp. 189-201 ◽  
Author(s):  
Jay Shankar ◽  
Cecile Boscher ◽  
Ivan R. Nabi
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Cancer Cell ◽  
Cellular Response ◽  
Spatial Organization ◽  
Essential Feature ◽  
Cell Signalling ◽  
Coated Pits ◽  
Signalling Molecules ◽  
Raft Domains

Spatial organization of the plasma membrane is an essential feature of the cellular response to external stimuli. Receptor organization at the cell surface mediates transmission of extracellular stimuli to intracellular signalling molecules and effectors that impact various cellular processes including cell differentiation, metabolism, growth, migration and apoptosis. Membrane domains include morphologically distinct plasma membrane invaginations such as clathrin-coated pits and caveolae, but also less well-defined domains such as lipid rafts and the galectin lattice. In the present chapter, we will discuss interaction between caveolae, lipid rafts and the galectin lattice in the control of cancer cell signalling.

Comparison and Analysis of Computational Methods for Identifying N6 - methyladenosine Sites in Saccharomyces Cerevisiae

2020 ◽  
Vol 26 ◽  
Author(s):  
Pengmian Feng ◽  
Lijing Feng ◽  
Chaohui Tang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Computational Methods ◽  
Computational Analysis ◽  
Computational Prediction ◽  
Experimental Methods ◽  
Biological Processes ◽  
Biological Functions ◽  
Precise Location ◽  
Future Directions ◽  
The Past

Background and Purpose: N 6 -methyladenosine (m6A) plays critical roles in a broad set of biological processes. Knowledge about the precise location of m6A site in the transcriptome is vital for deciphering its biological functions. Although experimental techniques have made substantial contributions to identify m6A, they are still labor intensive and time consuming. As good complements to experimental methods, in the past few years, a series of computational approaches have been proposed to identify m6A sites. Methods: In order to facilitate researchers to select appropriate methods for identifying m6A sites, it is necessary to give a comprehensive review and comparison on existing methods. Results: Since researches on m6A in Saccharomyces cerevisiae are relatively clear, in this review, we summarized recent progresses on computational prediction of m6A sites in S. cerevisiae and assessed the performance of existing computational methods. Finally, future directions of computationally identifying m6A sites were presented. Conclusion: Taken together, we anticipate that this review will provide important guides for computational analysis of m 6A modifications.

Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Saleh A. Almatroodi ◽  
Mansoor Ali Syed ◽  
Arshad Husain Rahmani
Keyword(s):  
Clinical Trials ◽  
Cancer Cells ◽  
Active Compound ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Cell Signalling ◽  
Chemopreventive Agents ◽  
Signalling Molecules ◽  
Cancer Management ◽  
Induced Apoptosis

Background:: Curcumin, an active compound of turmeric spice is one of the most-studies natural compounds and have been widely recognized as chemopreventive agents. Several molecular mechanisms have been proven, curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as inhibition of carcinogenesis process. Objective:: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. Methods:: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed central and Google scholar for the implication of curcumin in cancer management along with special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com and www.freshpatents.com. Result:: Recent studies based on cancer cells have proven that curcumin have potential effects against cancer cells, prevent the growth of cancer and act as cancer therapeutic agents. Besides, curcumin exerted anticancer effects through inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. Conclusion:: Accumulating evidences suggest that curcumin has potentiality to inhibit cancer growth, induced apoptosis and modulate various cell signalling pathways molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy and safe dose in the management of various cancers.

Techniques to examine nucleotide binding by pseudokinases

2013 ◽  
Vol 41 (4) ◽  
pp. 975-980 ◽  
Author(s):  
Isabelle S. Lucet ◽  
Jeffrey J. Babon ◽  
James M. Murphy
Keyword(s):  
Signal Transduction ◽  
Drug Targets ◽  
Nucleotide Binding ◽  
Biological Functions ◽  
Binding Properties ◽  
Catalytic Activities ◽  
Functional Studies ◽  
Signalling Molecules ◽  
Advantages And Disadvantages ◽  
Human Kinome

Approximately 10% of the human kinome has been classified as pseudokinases due to the absence of one or more of three motifs known to play key roles in the catalytic activities of protein kinases. Structural and functional studies are now emerging, reclassifying this ‘dead’ kinase family as essential signalling molecules that act as crucial modulators of signal transduction. This raises the prospect that pseudokinases may well represent an as-yet-unexplored class of drug targets. However, the extent to which nucleotide binding and catalytic activity contribute to the biological functions of pseudokinases remains an area of great controversy. In the present review, we discuss the advantages and disadvantages of the different methods employed to characterize the nucleotide-binding properties and activity of pseudokinases.

scholarly journals Novel Substrates for Kinases Involved in the Biosynthesis of Inositol Pyrophosphates and Their Enhancement of ATPase Activity of a Kinase

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3601
Author(s):  
Raja Mohanrao ◽  
Ruth Manorama ◽  
Shubhra Ganguli ◽  
Mithun C. Madhusudhanan ◽  
Rashna Bhandari ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Catalytic Domain ◽  
Inositol Phosphate ◽  
Substrate Recognition ◽  
Competitive Inhibitor ◽  
Inositol Polyphosphates ◽  
Inositol Pyrophosphate ◽  
Phosphate Donor ◽  
Inositol Pyrophosphates

IP6K and PPIP5K are two kinases involved in the synthesis of inositol pyrophosphates. Synthetic analogs or mimics are necessary to understand the substrate specificity of these enzymes and to find molecules that can alter inositol pyrophosphate synthesis. In this context, we synthesized four scyllo-inositol polyphosphates—scyllo-IP5, scyllo-IP6, scyllo-IP7 and Bz-scyllo-IP5—from myo-inositol and studied their activity as substrates for mouse IP6K1 and the catalytic domain of VIP1, the budding yeast variant of PPIP5K. We incubated these scyllo-inositol polyphosphates with these kinases and ATP as the phosphate donor. We tracked enzyme activity by measuring the amount of radiolabeled scyllo-inositol pyrophosphate product formed and the amount of ATP consumed. All scyllo-inositol polyphosphates are substrates for both the kinases but they are weaker than the corresponding myo-inositol phosphate. Our study reveals the importance of axial-hydroxyl/phosphate for IP6K1 substrate recognition. We found that all these derivatives enhance the ATPase activity of VIP1. We found very weak ligand-induced ATPase activity for IP6K1. Benzoyl-scyllo-IP5 was the most potent ligand to induce IP6K1 ATPase activity despite being a weak substrate. This compound could have potential as a competitive inhibitor.

CRYPTIC CAUSES AND MECHANISMS INVOLVED IN AGEING

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (01) ◽  
pp. 5-22
Author(s):  
K Challabotla ◽  
◽  
D Banji ◽  
O.J.F Banji ◽  
Chilipi K Reddy
Keyword(s):  
Oxidative Stress ◽  
Developing Countries ◽  
Molecular Basis ◽  
Metabolic Disorders ◽  
Natural Process ◽  
Biological Functions ◽  
Stress Theory ◽  
Biochemical Alterations ◽  
Organ Systems ◽  
The Brain

Ageing is a natural process characterized by progressive deterioration of biological functions. Ageing causes both morphological as well as biochemical alterations in various body organs leading to deterioration of health. Proteins, enzymes and neurotransmitters are affected, which in turn can result in dysregulation of various pathways. WHO has reported that by 2020, three quarters of all deaths in developing countries will be age-associated. Currently more than 300 theories exist to explain the phenomenon of ageing; amongst them the oxidative stress theory of ageing is most studied and accepted for the molecular basis of ageing. All these processes can progress at an unprecedented pace on contact with triggering factors, leading to the development of pathological ageing. The probability of developing neurodegenerative and metabolic disorders is relatively high under such circumstances. This review emphasizes the theories and mechanisms of ageing and an overview on the aspects of age associated biochemical changes and the implications on the brain, liver and various organ systems.

Cwnt-8C: a novel Wnt gene with a potential role in primitive streak formation and hindbrain organization

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1147-1160 ◽  
Author(s):  
C.R. Hume ◽  
J. Dodd
Keyword(s):  
Gene Family ◽  
Potential Role ◽  
Marginal Zone ◽  
Cell Signalling ◽  
Primitive Streak ◽  
Axis Formation ◽  
Restricted Domain ◽  
Signalling Molecules ◽  
Wnt Proteins ◽  
Chick Embryogenesis

To begin to examine the possibility that Wnt proteins act as cell signalling molecules during chick embryogenesis, PCR was used to identify Wnt genes expressed in Hensen's node. We have identified a novel member of the Wnt gene family, Cwnt-8C, which is expressed prior to gastrulation in the posterior marginal zone, the primitive streak and Hensen's node. Injection of Cwnt-8C mRNA into Xenopus embryos caused axis duplication and dorsalization of mesodermal tissues. During neurulation, Cwnt-8C is expressed transiently in a restricted domain of the prospective hindbrain neurectoderm that will give rise to rhombomere 4. This domain is defined prior to the formation of rhombomere boundaries and also precedes the up-regulation and restriction of expression of Hox B1 in the same region. Thus, Cwnt-8C is potentially involved in the regulation of axis formation and hindbrain patterning.

Sign in / Sign up

Export Citation Format

Share Document