Regulation and cellular functions of class II phosphoinositide 3-kinases

2012 ◽  
Vol 443 (3) ◽  
pp. 587-601 ◽  
Author(s):  
Marco Falasca ◽  
Tania Maffucci
Keyword(s):  
Class Ii ◽  
Human Diseases ◽  
Present Review ◽  
Signalling Pathways ◽  
Cellular Functions ◽  
Functional Roles ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Downstream Effectors ◽  
Phosphoinositide 3 Kinase

Class II isoforms of PI3K (phosphoinositide 3-kinase) are still the least investigated and characterized of all PI3Ks. In the last few years, an increased interest in these enzymes has improved our understanding of their cellular functions. However, several questions still remain unanswered on their mechanisms of activation, their specific downstream effectors and their contribution to physiological processes and pathological conditions. Emerging evidence suggests that distinct PI3Ks activate different signalling pathways, indicating that their functional roles are probably not redundant. In the present review, we discuss the recent advances in our understanding of mammalian class II PI3Ks and the evidence suggesting their involvement in human diseases.

New insight into the intracellular roles of class II phosphoinositide 3-kinases

2014 ◽  
Vol 42 (5) ◽  
pp. 1378-1382 ◽  
Author(s):  
Tania Maffucci ◽  
Marco Falasca
Keyword(s):  
Class Ii ◽  
Present Review ◽  
Phosphoinositide 3 Kinase ◽  
Redundant Role ◽  
Insight Into

In the last few years, an increased attention to class II isoforms of phosphoinositide 3-kinase (PI3K) has emerged, mainly fuelled by evidence suggesting a distinct non-redundant role for these enzymes compared with other PI3Ks. Despite this renewed interest, many questions remain on the specific functions regulated by these isoforms and their mechanism of activation and action. In the present review, we discuss results from recent studies that have provided some answers to these questions.

scholarly journals Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration

2005 ◽  
Vol 169 (5) ◽  
pp. 789-799 ◽  
Author(s):  
Tania Maffucci ◽  
Frank T. Cooke ◽  
Fiona M. Foster ◽  
Colin J. Traer ◽  
Michael J. Fry ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathway ◽  
Lysophosphatidic Acid ◽  
Second Messenger ◽  
Cellular Responses ◽  
Class Ii ◽  
Downstream Effectors ◽  
Phosphoinositide 3 Kinase ◽  
Precise Role

The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many cellular responses such as proliferation, migration, and survival. Disregulation of PI3K-activated pathways is implicated in different diseases including cancer and diabetes. Among the three classes of PI3Ks, class I is the best characterized, whereas class II has received increasing attention only recently and the precise role of these isoforms is unclear. Similarly, the role of phosphatidylinositol-3-phosphate (PtdIns-3-P) as an intracellular second messenger is only just beginning to be appreciated. Here, we show that lysophosphatidic acid (LPA) stimulates the production of PtdIns-3-P through activation of a class II PI3K (PI3K-C2β). Both PtdIns-3-P and PI3K-C2β are involved in LPA-mediated cell migration. This study is the first identification of PtdIns-3-P and PI3K-C2β as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K. Defining this novel PI3K-C2β–PtdIns-3-P signaling pathway may help clarify the process of cell migration and may shed new light on PI3K-mediated intracellular events.

scholarly journals Hypoxia-Induced Mitogenic Factor: A Multifunctional Protein Involved in Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Moyang Lv ◽  
Wenjuan Liu
Keyword(s):  
Clinical Significance ◽  
Metabolic Disorders ◽  
Critical Role ◽  
Present Review ◽  
Molecular Characteristics ◽  
Multifunctional Protein ◽  
Mitogenic Factor ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Health And Disease

Hypoxia-induced mitogenic factor (HIMF), also known as resistin-like molecule α (RELMα) or found in inflammatory zone 1 (FIZZ1) is a member of the RELM protein family expressed in mice. It is involved in a plethora of physiological processes, including mitogenesis, angiogenesis, inflammation, and vasoconstriction. HIMF expression can be stimulated under pathological conditions and this plays a critical role in pulmonary, cardiovascular and metabolic disorders. The present review summarizes the molecular characteristics, and the physiological and pathological roles of HIMF in normal and diseased conditions. The potential clinical significance of these findings for human is also discussed.

Pathophysiological Functions of the lncRNA TUG1

2020 ◽  
Vol 26 (6) ◽  
pp. 688-700 ◽  
Author(s):  
Chong Guo ◽  
Yuying Qi ◽  
Jiayuan Qu ◽  
Liyue Gai ◽  
Yue Shi ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Human Cancer ◽  
Human Diseases ◽  
Biological Processes ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
Therapy Targets ◽  
Physiological Processes ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Background: Long non-coding RNAs (lncRNAs) with little or no coding capacity are associated with a plethora of cellular functions, participating in various biological processes. Cumulative study of lncRNA provides explanations to the physiological and pathological processes and new perspectives to the diagnosis, prevention, and treatment of some clinical diseases. Long non-coding RNA taurine-upregulated gene 1(TUG1) is one of the first identified lncRNAs associated with human disease, which actively involved in various physiological processes, including regulating genes at epigenetics, transcription, post-transcription, translation, and posttranslation. The aim of this review was to explore the molecular mechanism of TUG1 in various types of human diseases. Methods: In this review, we summarized and analyzed the latest findings related to the physiologic and pathophysiological processes of TUG1 in human diseases. The related studies were retrieved and selected the last six years of research articles in PubMed with lncRNA and TUG1 as keywords. Results: TUG1 is a valuable lncRNA that its dysregulated expression and regulating the biological processes were found in a variety of human diseases. TUG1 is found to exhibit aberrant expression in a variety of malignancies. Dysregulation of TUG1 has been shown to contribute to proliferation, migration, cell cycle changes, inhibited apoptosis, and drug resistance of cancer cells, which revealed an oncogenic role for this lncRNA, but some reports have shown downregulation of TUG1 in lung cancer samples compared with noncancerous samples. In addition, the molecular and biological functions of TUG1 in physiology and disease (relevant to endocrinology, metabolism, immunology, neurobiology) have also been highlighted. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of TUG1 in cancer and other diseases. Conclusion: Long non-coding RNA-TUG1 likely served as useful disease biomarkers or therapy targets and effectively applied in different kinds of diseases, such as human cancer and cardiovascular diseases.

Protein partners of the calcium channel β subunit highlight new cellular functions

2016 ◽  
Vol 473 (13) ◽  
pp. 1831-1844 ◽  
Author(s):  
Mohamad Rima ◽  
Marwa Daghsni ◽  
Ziad Fajloun ◽  
Ridha M'rad ◽  
Juan L. Brusés ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Signalling ◽  
Β Subunit ◽  
Cellular Functions ◽  
Excitable Cells ◽  
Functional Roles ◽  
Physiological Processes ◽  
Protein Partners ◽  
Wide Range

Calcium plays a key role in cell signalling by its intervention in a wide range of physiological processes. Its entry into cells occurs mainly via voltage-gated calcium channels (VGCC), which are found not only in the plasma membrane of excitable cells but also in cells insensitive to electrical signals. VGCC are composed of different subunits, α1, β, α2δ and γ, among which the cytosolic β subunit (Cavβ) controls the trafficking of the channel to the plasma membrane, its regulation and its gating properties. For many years, these were the main functions associated with Cavβ. However, a growing number of proteins have been found to interact with Cavβ, emphasizing the multifunctional role of this versatile protein. Interestingly, some of the newly assigned functions of Cavβ are independent of its role in the regulation of VGCC, and thus further increase its functional roles. Based on the identity of Cavβ protein partners, this review emphasizes the diverse cellular functions of Cavβ and summarizes both past findings as well as recent progress in the understanding of VGCC.

Extraction of Essential Oils from Medicinal Plants and their Utilization as Food Antioxidants

2020 ◽  
Vol 26 (5) ◽  
pp. 519-541 ◽  
Author(s):  
Giovanna Ferrentino ◽  
Ksenia Morozova ◽  
Christine Horn ◽  
Matteo Scampicchio
Keyword(s):  
Chemical Composition ◽  
Medicinal Plants ◽  
Beneficial Effect ◽  
Essential Oils ◽  
Bioactive Compounds ◽  
Antimicrobial Properties ◽  
Food Products ◽  
Human Diseases ◽  
Present Review ◽  
Green Technologies

Background: The use of essential oils is receiving increasing attention worldwide, as these oils are good sources of several bioactive compounds. Nowadays essential oils are preferred over synthetic preservatives thanks to their antioxidant and antimicrobial properties. Several studies highlight the beneficial effect of essential oils extracted from medicinal plants to cure human diseases such as hypertension, diabetes, or obesity. However, to preserve their bioactivity, the use of appropriate extraction technologies is required. Method: The present review aims to describe the studies published so far on the essential oils focusing on their sources and chemical composition, the technologies used for their recovery and their application as antioxidants in food products. Results: The review has been structured in three parts. In the first part, the main compounds present in essential oils extracted from medicinal plants have been listed and described. In the second part, the most important technologies used for extraction and distillation, have been presented. In detail, conventional methods have been described and compared with innovative and green technologies. Finally, in the last part, the studies related to the application of essential oils as antioxidants in food products have been reviewed and the main findings discussed in detail. Conclusions: In summary, an overview of the aforementioned subjects is presented by discussing the results of the most recent published studies.

scholarly journals Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

2021 ◽  
Vol 3 (2) ◽  
pp. 312-341
Author(s):  
Maria Neus Ballester Roig ◽  
Tanya Leduc ◽  
Cassandra C. Areal ◽  
Valérie Mongrain
Keyword(s):  
Sleep Time ◽  
Sleep Regulation ◽  
Neuronal Communication ◽  
Cellular Effects ◽  
Pathological Conditions ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Cellular Pathways ◽  
Phosphoinositide 3 Kinase ◽  
Protein Kinase Akt

Uncaria rhynchophylla is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing Uncaria ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions. Rhynchophylline (Rhy) is one of the principal alkaloids in Uncaria species. Although treatment with Rhy alone has not been tested in humans, observations in rodents show that Rhy increases sleep time. However, the mechanisms by which Rhy could modulate sleep have not been comprehensively described. In this review, we are highlighting cellular pathways that are shown to be targeted by Rhy and which are also known for their implications in the regulation of wakefulness and sleep. We conclude that Rhy can impact sleep through mechanisms involving ion channels, N-methyl-d-aspartate (NMDA) receptors, tyrosine kinase receptors, extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT), and nuclear factor-kappa B (NF-κB) pathways. In modulating multiple cellular responses, Rhy impacts neuronal communication in a way that could have substantial effects on sleep phenotypes. Thus, understanding the mechanisms of action of Rhy will have implications for sleep pharmacology.

scholarly journals Impaired platelet responses to thrombin and collagen in AKT-1–deficient mice

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1703-1710 ◽  
Author(s):  
Juhua Chen ◽  
Sarmishtha De ◽  
Derek S. Damron ◽  
William S. Chen ◽  
Nissim Hay ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Dense Granules ◽  
Fibrinogen Binding ◽  
Downstream Effectors ◽  
Low Concentrations ◽  
Phosphoinositide 3 Kinase ◽  
Deficient Mice ◽  
Granule Release

Abstract We investigated the role of Akt-1, one of the major downstream effectors of phosphoinositide 3-kinase (PI3K), in platelet function using mice in which the gene for Akt-1 had been inactivated. Using ex vivo techniques, we showed that Akt-1-deficient mice exhibited impaired platelet aggregation and spreading in response to various agonists. These differences were most apparent in platelets activated with low concentrations of thrombin. Although Akt-1 is not the predominant Akt isoform in mouse platelets, its absence diminished the amount of total phospho-Akt and inhibited increases in intracellular Ca2+ concentration in response to thrombin. Moreover, thrombin-induced platelet α-granule release as well as release of adenosine triphosphate from dense granules was also defective in Akt-1-null platelets. Although the absence of Akt-1 did not influence expression of the major platelet receptors for thrombin and collagen, fibrinogen binding in response to these agonists was significantly reduced. As a consequence of impaired αIIbβ3 activation and platelet aggregation, Akt-1 null mice showed significantly longer bleeding times than wild-type mice. (Blood. 2004;104:1703-1710)

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