Results for 'AMP‐activated protein kinase'

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  1.  8
    AMP‐activated protein kinase ‐ An archetypal protein kinase cascade?D. Grahame Hardie & Robert W. Mackintosh - 1992 - Bioessays 14 (10):699-704.
    Mammalian AMP‐activated protein kinase is the central component of a protein kinase cascade which inactivates three key enzymes involved in the synthesis or release of free fatty acids and cholesterol inside the cell. The kinase cascade is activated by elevation of AMP, and perhaps also by fatty acid and cholesterol metabolites. The system may fulfil a protective function, preventing damage caused by depletion of ATP or excessive intracellular release of free lipids, a type of (...)
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  2.  29
    Expanding roles for AMP‐activated protein kinase in neuronal survival and autophagy.Jeroen Poels, Miloš R. Spasić, Patrick Callaerts & Koenraad K. Norga - 2009 - Bioessays 31 (9):944-952.
    AMP‐activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti‐diabetic drugs, exerts its actions by AMPK activation. However, while (...)
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  3.  29
    AMP‐activated protein kinase: the energy charge hypothesis revisited.D. Grahame Hardie & Simon A. Hawley - 2001 - Bioessays 23 (12):1112-1119.
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  4.  19
    Surviving Starvation: AMPK Protects Germ Cell Integrity by Targeting Multiple Epigenetic Effectors.Emilie Demoinet & Richard Roy - 2018 - Bioessays 40 (3):1700095.
    Acute starvation can have long-term consequences that are mediated through epigenetic change. Some of these changes are affected by the activity of AMP-activated protein kinase, a master regulator of cellular energy homeostasis. In Caenorhabditis elegans, the absence of AMPK during a period of starvation in an early larval stage results in developmental defects following their recovery on food, while many of them become sterile. Moreover, the loss of AMPK during this quiescent period results in transgenerational phenotypes that can (...)
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  5.  17
    Hypothalamic fatty acid metabolism: A housekeeping pathway that regulates food intake.Miguel López, Christopher J. Lelliott & Antonio Vidal-Puig - 2007 - Bioessays 29 (3):248-261.
    The hypothalamus is a specialized area in the brain that integrates the control of energy homeostasis. More than 70 years ago, it was proposed that the central nervous system sensed circulating levels of metabolites such as glucose, lipids and amino acids and modified feeding according to the levels of those molecules. This led to the formulation of the Glucostatic, Lipostatic and Aminostatic Hypotheses. It has taken almost that much time to demonstrate that circulating long‐chain fatty acids act as signals of (...)
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  6.  23
    The LKB1‐AMPK and mTORC1 Metabolic Signaling Networks in Schwann Cells Control Axon Integrity and Myelination.Bogdan Beirowski - 2019 - Bioessays 41 (1):1800075.
    The Liver kinase B1 with its downstream target AMP activated protein kinase (LKB1‐AMPK), and the key nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) form two signaling systems that coordinate metabolic and cellular activity with changes in the environment in order to preserve homeostasis. For example, nutritional fluctuations rapidly feed back on these signaling systems and thereby affect cell‐specific functions. Recent studies have started to reveal important roles of these strategic metabolic regulators in Schwann cells for (...)
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  7.  10
    Protein kinase cascades activated by stress and inflammatory cytokines.John M. Kyriakis & Joseph Avruch - 1996 - Bioessays 18 (7):567-577.
    Signal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being a member of the extracellular signal‐regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by the inflammatory cytokines TNF‐α and IL‐1‐β, as well as by a wide variety of cellular stresses such as UV and ionizing radiation, hyperosmolarity, heat stress, oxidative stress, etc. One pathway converges on the ERK subfamily known as the ‘stress activated’ (...)
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  8.  20
    The Rho GTPase regulates protein kinase activity.Koh-Ichi Nagata & Alan Hall - 1996 - Bioessays 18 (7):529-531.
    Rho, a member of the Ras superfamily of small GTPases, has multiple biological roles: it regulates signal trasduction pathways linking extracellular growth factors to the assembly of actin stress fibres and focal adhesion complexes; it is required for G1 progression and activates the SRF transcription factor when quiescent fibroblasts are stimulated to grow; and it plays a role later in the cell cycle during cytokinesis. Two groups have recently succeeded in identifying downstream effectors of Rho that may mediate some of (...)
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  9.  13
    Calmodulin‐dependent protein kinase II.Hitoshi Fujisawa - 1990 - Bioessays 12 (1):27-29.
    Three multifunctional protein kinases, cyclic AMP‐dependent protein kinase, protein kinase C, and calmodulin‐dependent protein kinase II, are involved in signal transduction in response to their respective second messengers, cyclic AMP, diacylglycerol, and Ca2+. This review will summarize the key findings on calmodulin‐dependent protein kinase II.
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  10.  10
    It Takes Two to Tango: Activation of Protein Kinase D by Dimerization.Ronja Reinhardt, Linda Truebestein, Heiko A. Schmidt & Thomas A. Leonard - 2020 - Bioessays 42 (4):1900222.
    The recent discovery and structure determination of a novel ubiquitin‐like dimerization domain in protein kinase D (PKD) has significant implications for its activation. PKD is a serine/threonine kinase activated by the lipid second messenger diacylglycerol (DAG). It is an essential and highly conserved protein that is implicated in plasma membrane directed trafficking processes from the trans‐Golgi network. However, many open questions surround its mechanism of activation, its localization, and its role in the biogenesis of cargo transport (...)
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  11.  9
    Protein kinases: A diverse family of related proteins.Susan S. Taylor - 1987 - Bioessays 7 (1):24-29.
    Homologies in amino‐acid sequence indicate that all known protein kinases share a conserved catalytic core, and, thus, belong to a related family of proteins that have evolved in part from a common ancestoral origin. This family includes cellular kinases, oncogenic viral kinases and their protooncogene counterparts, and growth factor receptors. One of the simplest and certainly the best characterized of the protein kinases at the biochemical level is the kinase that is activated in response to cAMP. The (...)
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  12.  9
    Growth‐related protein kinases.Ray K. Ralph, Sandra Darkin-Rattray & Phillip Schofield - 1990 - Bioessays 12 (3):121-124.
    A protein kinase cascade is involved in the action of some mitogens. The cascade begins with receptor tyrosine kinase activation by growth factors. The resulting signal is transmitted into cells via phospholipid metabolism which produces a variety of second messengers and by intracellular protein kinase activation. The signal is then propagated and disseminated via a network of other proteln kinases and protein phosphatases. Recent research suggests that ribosomal protein S6 kinase and casein (...)
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  13.  26
    Cyclin‐dependent protein kinases: Key regulators of the eukaryotic cell cycle.Erich A. Nigg - 1995 - Bioessays 17 (6):471-480.
    Passage through the cell cycle requires the successive activation of different cyclin‐dependent protein kinases (CDKs). These enzymes are controlled by transient associations with cyclin regulatory subunits, binding of inhibitory polypeptides and reversible phosphorylation reactions. To promote progression towards DNA replication, CDK/cyclin complexes phosphorylate proteins required for the activation of genes involved in DNA synthesis, as well as components of the DNA replication machinery. Subsequently, a different set of CDK/cyclin complexes triggers the phosphorylation of numerous proteins to promote the profound (...)
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  14.  24
    cAMP‐dependent protein kinase A and the dynamics of epithelial cell surface domains: Moving membranes to keep in shape.Kacper A. Wojtal, Dick Hoekstra & Sven C. D. van IJzendoorn - 2008 - Bioessays 30 (2):146-155.
    Cyclic adenosine monophosphate (cAMP) and cAMP‐dependent protein kinase A (PKA) are evolutionary conserved molecules with a well‐established position in the complex network of signal transduction pathways. cAMP/PKA‐mediated signaling pathways are implicated in many biological processes that cooperate in organ development including the motility, survival, proliferation and differentiation of epithelial cells. Cell surface polarity, here defined as the anisotropic organisation of cellular membranes, is a critical parameter for most of these processes. Changes in the activity of cAMP/PKA elicit a (...)
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  15.  8
    Drosophila WARTS–tumor suppressor and member of the myotonic dystrophy protein kinase family.Kellie L. Watson - 1995 - Bioessays 17 (8):673-676.
    Tumor suppressor genes represent a broad class of genes that normally function in the negative regulation of cell proliferation. Loss‐of‐function mutations in these genes lead to unrestrained cell proliferation and tumor formation. A fundamental understanding of how tumor suppressor genes regulate cell proliferation and differentiation should reveal important aspects of signalling pathways and cell cycle control. A recent report describing the Drosophila tumor suppressor gene warts has implications in the study of the human myotonic dystrophy gene(1). These genes encode members (...)
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  16.  22
    Checkpoint signaling: Epigenetic events sound the DNA strand‐breaks alarm to the ATM protein kinase.Robert T. Abraham - 2003 - Bioessays 25 (7):627-630.
    The ATM protein kinase is centrally involved in the cellular response to ionizing radiation (IR) and other DNA double‐strand‐break‐inducing insults. Although it has been well established that IR exposure activates the ATM kinase domain, the actual mechanism by which ATM responds to damaged DNA has remained enigmatic. Now, a landmark paper provides strong evidence that DNA‐strand breaks trigger widespread activation of ATM through changes in chromatin structure.1 This review discusses a checkpoint activation model in which chromatin perturbations (...)
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  17.  8
    Harnessing the cooperation between DNA‐PK and cGAS in cancer therapies.Clara Taffoni, Moritz Schüssler, Isabelle K. Vila & Nadine Laguette - 2023 - Bioessays 45 (7):2300045.
    The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory responses (...)
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  18.  19
    Signaling molecules in regenerating hydra.Brigitte Galliot - 1997 - Bioessays 19 (1):37-46.
    Ever since it was discovered in hydra, regeneration has remained a stimulating question for developmental biologists. Cellular approaches have revealed that, within the first few hours of apical or basal hydra regeneration, differentiation and determination of nerve cells are the primary cellular events detectable. The head and foot activators (HA, FA), neuropeptides that are released upon injury, are signaling molecules involved in these processes. In conditions where it induces cellular differentiation or determination, HA behaves as an agonist of the cyclic (...)
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  19.  3
    Oncogene homologues in yeast.A. E. Wheals - 1985 - Bioessays 3 (3):108-112.
    Two different yeasts have a number of genes bearing striking structural and functional homologies to mammalian oncogenes. In yeast these genes are involved in the control of proliferation and early steps in the cell cycle. Many have putative protein kinase activity and some have been shown to control the activity of the enzyme adenylate cyclase which synthesizes cyclic AMP. Mutant forms of these yeast genes have oncogenic activity in mammalian cells.
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  20.  29
    Do the calmodulin-stimulated adenylyl cyclases play a role in neuroplasticity?Zhengui Xia, Eui-Ju Choi, Daniel R. Storm & Christine Blazynski - 1995 - Behavioral and Brain Sciences 18 (3):429-440.
    Evidence from invertebrate systems including Aplysia and Drosophila, as well as studies carried out with mammalian brain, suggests that Ca2+-sensitive adenylyl cyclases may be important for long-term synaptic changes and learning and memory. Furthermore, some forms of long-term potentiation (LTP) in the hippocampus elevate cyclic AMP (cAMP) signals, and activation of adenylyl cyclases and cAMP-dependent protein kinase may be required for late stages of LTP. We propose that long-term changes in neurons and at synapses may require synergism between (...)
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  21.  10
    Regulation of meiosis: From DNA binding protein to protein kinase.Maureen McLeod - 1989 - Bioessays 11 (1):9-14.
    The transition from mitotic cell division to meiosis in yeast is governed by both the mating‐type genes and signals from the environment. Analysis of mutants that are unable to regulate entry into meiosis has identified many genes that function in this process and in some cases, the biochemical activity of their protein products has been described. At least two of the the mating‐type genes of Saccharomyces cerevisiae encode DNA binding proteins that regulate transcription of unlinked genes required for entry (...)
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  22.  7
    Scaffold proteins in MAP kinase signaling: more than simple passive activating platforms.Nicolas Dard & Matthias Peter - 2006 - Bioessays 28 (2):146-156.
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  23.  15
    The DAP kinase family of pro‐apoptotic proteins: novel players in the apoptotic game.Donat Kögel, Jochen H. M. Prehn & Karl Heinz Scheidtmann - 2001 - Bioessays 23 (4):352-358.
    The DAP (Death Associated Protein) kinase family is a novel subfamily of pro-apoptotic serine/threonine kinases. All five DAP kinase family members identified to date are ubiquitously expressed in various tissues and are capable of inducing apoptosis. The sequence homology of the five kinases is largely restricted to the N-terminal kinase domain. In contrast, the adjacent C-terminal regions are very diverse and link individual family members to specific signal transduction pathways. There is increasing evidence that DAP (...) family members are involved in both extrinsic and intrinsic pathways of apoptosis and may play a role in tumor progression. This review will focus on structural composition and subcellular localization of DAP kinase family members and on signal transduction pathways leading to their activation. Potential mechanisms of DAP kinase family-mediated apoptosis will be discussed. BioEssays 23:352–358, 2001. © 2001 John Wiley & Sons, Inc. (shrink)
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  24.  11
    Kinases and G proteins join the Wnt receptor complex.Tom Quaiser, Roman Anton & Michael Kühl - 2006 - Bioessays 28 (4):339-343.
    Wnt proteins form a family of secreted signaling proteins that play a key role in various developmental events such as cell differentiation, cell migration, cell polarity and cell proliferation. It is currently thought that Wnt proteins activate at least three different signaling pathways by binding to seven transmembrane receptors of the Frizzled family and the co-receptor LRP6. Despite our growing knowledge of intracellular components that mediate a Wnt signal, the molecular events at the membrane have remained rather unclear. Now several (...)
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  25.  7
    Integrating the MAP kinase signal into the G1 phase cell cycle machinery.Kristin Roovers & Richard K. Assoian - 2000 - Bioessays 22 (9):818-826.
    Growth factors and the extracellular matrix provide the environmental cues that control the proliferation of most cell types. The binding of growth factors and matrix proteins to receptor tyrosine kinases and integrins, respectively, regulates several cytoplasmic signal transduction cascades, among which activation of the mitogen-activated protein kinase cascade, ras → Raf → MEK → ERK, is perhaps the best characterized. Curiously, ERK activation has been associated with both stimulation and inhibition of cell proliferation. In this review, we summarize (...)
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  26.  18
    The isoform‐specific functions of the c‐Jun N‐terminal Kinases (JNKs): differences revealed by gene targeting.Marie A. Bogoyevitch - 2006 - Bioessays 28 (9):923-934.
    The c‐Jun N‐terminal kinases (JNKs) are members of the mitogen‐activated protein kinase (MAPK) family. In mammalian genomes, three genes encode the JNK family. To evaluate JNK function, mice have been created with deletions in one or more of three Jnk genes. Initial studies on jnk1−/− or jnk2−/− mice have shown roles for these JNKs in the immune system whereas studies on jnk3−/− mice have highlighted roles for JNK3 in the nervous system. Further studies have highlighted the contributions of (...)
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  27.  21
    Non‐kinase second‐messenger signaling: new pathways with new promise.Gregory M. Springett, Hiroaki Kawasaki & David R. Spriggs - 2004 - Bioessays 26 (7):730-738.
    Intercellular signaling by growth factors, hormones and neurotransmitters produces second messenger molecules such as cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG). Protein Kinase A and Protein Kinase C are the principal effector proteins of these prototypical second messengers in certain cell types. Recently, novel receptors for cAMP and DAG have been identified. These proteins, designated EPAC (Exchange Protein directly Activated by cAMP) or cAMP‐GEF (cAMP regulated Guanine nucleotide Exchange Factor) and CalDAG‐GEF (Calcium and Diacylglycerol regulated (...)
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  28.  7
    Structural and functional diversity of adaptor proteins involved in tyrosine kinase signalling.Ágnes Csiszár - 2006 - Bioessays 28 (5):465-479.
    Adaptors are proteins of multi‐modular structure without enzymatic activity. Their capacity to organise large, temporary protein complexes by linking proteins together in a regulated and selective fashion makes them of outstanding importance in the establishment and maintenance of specificity and efficiency in all known signal transduction pathways. This review focuses on the structural and functional characterisation of adaptors involved in tyrosine kinase (TK) signalling. TK‐linked adaptors can be distinguished by their domain composition and binding specificities. However, such structural (...)
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  29.  53
    G protein‐coupled receptors engage the mammalian Hippo pathway through F‐actin.Laura Regué, Fan Mou & Joseph Avruch - 2013 - Bioessays 35 (5):430-435.
    The Hippo pathway, a cascade of protein kinases that inhibits the oncogenic transcriptional coactivators YAP and TAZ, was discovered in Drosophila as a major determinant of organ size in development. Known modes of regulation involve surface proteins that mediate cell‐cell contact or determine epithelial cell polarity which, in a tissue‐specific manner, use intracellular complexes containing FERM domain and actin‐binding proteins to modulate the kinase activities or directly sequester YAP. Unexpectedly, recent work demonstrates that GPCRs, especially those signaling through (...)
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  30.  17
    Activation of mammalian gene expression by the UV component of sunlight – from models to reality.Rex M. Tyrrell - 1996 - Bioessays 18 (2):139-148.
    Ultraviolet radiation activates the expression of a wide variety of genes, by pathways which differ between the short non‐solar ultraviolet C (UVC) wavelengths, which are strongly absorbed by nucleic acids, and the long solar ultraviolet A (UVA, 320–380 nm) wavelengths, which generate active oxygen intermediates. Intermediate solar ultraviolet (UV) wavelengths in the UVB (290–320 nm) range also contain an oxidative component, but more closely resemble UVC in their gene activating properties. Short wavelength UV, in common with other extracellular stimuli including (...)
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  31.  10
    Deceiving appearances: signaling by “dead” and “fractured” receptor protein-tyrosine kinases.Michael Kroiher, Michael A. Miller & Robert E. Steele - 2001 - Bioessays 23 (1):69-76.
    The mechanisms by which most receptor protein‐tyrosine kinases (RTKs) transmit signals are now well established. Binding of ligand results in the dimerization of receptor monomers followed by transphosphorylation of tyrosine residues within the cytoplasmic domains of the receptors. This tidy picture has, however, some strange characters lurking around the edges. Cases have now been identified in which RTKs lack kinase activity, but, despite being “dead” appear to have roles in signal transduction. Even stranger are the cases in which (...)
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  32.  12
    Control of phosphatidylinositol‐3‐kinase signaling by nanoscale membrane compartmentalization.Rebecca Cabral-Dias & Costin N. Antonescu - 2023 - Bioessays 45 (3):2200196.
    Phosphatidylinositol‐3‐kinases (PI3Ks) are lipid kinases that produce 3‐phosphorylated derivatives of phosphatidylinositol upon activation by various cues. These 3‐phosphorylated lipids bind to various protein effectors to control many cellular functions. Lipid phosphatases such as phosphatase and tensin homolog (PTEN) terminate PI3K‐derived signals and are critical to ensure appropriate signaling outcomes. Many lines of evidence indicate that PI3Ks and PTEN, as well as some specific lipid effectors are highly compartmentalized, either in plasma membrane nanodomains or in endosomal compartments. We examine the (...)
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  33.  7
    Cytokine signal transduction and the JAK family of protein tyrosine kinases.Andrew F. Wilks & Ailsa G. Harpur - 1994 - Bioessays 16 (5):313-320.
    Cytokine receptors fall into two basic classes: those with their own intrinsic protein tyrosine kinase (PTK) domain, and those lacking a PTK domain. Nonetheless, PTK activity plays a fundamental role in the signal transduction processes lying downstream of both classes of receptor. It now seems likely that many of those cytokine receptors that lack their own PTK domain use members of the JAK family of PTKs to propagate their intracellular signals. Moreover, the involvement of the JAK kinases in (...)
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  34.  14
    Signaling through focal adhesion kinase.Steven K. Hanks & Thomas R. Polte - 1997 - Bioessays 19 (2):137-145.
    Focal adhesion kinase (FAK) is a nonreceptor protein‐tyrosine kinase implicated in controlling cellular responses to the engagement of cell‐surface integrins, including cell spreading and migration, survival and proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v‐Src. Progress toward elucidating the events leading to FAK activation following integrin‐mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and interacting proteins. A signaling (...)
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  35.  8
    Protein Phosphorylation Dynamics: Unexplored Because of Current Methodological Limitations.Alain Robichon - 2020 - Bioessays 42 (4):1900149.
    The study of intrinsic phosphorylation dynamics and kinetics in the context of complex protein architecture in vivo has been challenging: Method limitations have prevented significant advances in the understanding of the highly variable turnover of phosphate groups, synergy, and cooperativity between P‐sites. However, over the last decade, powerful analytical technologies have been developed to determine the full catalog of the phosphoproteome for many species. The curated databases of phospho sites found by mass spectrometry analysis and the computationally predicted sites (...)
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  36.  19
    PuF, an antimetastatic and developmental signaling protein, interacts with the Alzheimer's amyloid-beta precursor protein via a tissue-specific proximal regulatory element.D. K. Lahiri, B. Maloney, J. T. Rogers & Y. W. Ge - 2013 - Bmc Genomics 14:68.
    BACKGROUND: Alzheimer's disease is intimately tied to amyloid-beta peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein account for a small proportion of AD cases, suggesting that regulation of the associated gene may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" , at -76/-47, (...)
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  37.  21
    Regulation of zygotic gene activation in the mouse.Richard M. Schultz - 1993 - Bioessays 15 (8):531-538.
    Zygotic gene activation (ZGA) is the critical event that governs the transition from maternal to embryonic control of development. In the mouse, ZGA occurs during the 2‐cell stage and appears to be regulated by the time following fertilization, i.e. a zygotic clock, rather than by progression through the first cell cycle. The onset of ZGA must depend on maternally inherited proteins, and post‐translational modification of these maternally derived proteins is likely to play a role in ZGA. Consistent with this prediction (...)
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  38.  20
    The secreted kinase ROP18 defends Toxoplasma's border.Sarah J. Fentress & L. David Sibley - 2011 - Bioessays 33 (9):693-700.
    Toxoplasma gondii is a highly successful parasite capable of infecting virtually all warm-blooded animals by actively invading nucleated host cells and forming a modified compartment where it replicates within the cytosol. The parasite-containing vacuole provides a safe haven, even in professional phagocytes such as macrophages, which normally destroy foreign microbes. In an effort to eliminate the parasite, the host up-regulates a family of immunity-related p47 GTPases (IRGs), which are recruited to the parasite-containing vacuole, resulting in membrane rupture and digestion of (...)
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  39.  14
    Vav: A potential link between tyrosine kinases and Ras‐like GTPases in hematopoietic cell signaling.Patrick Hu, Ben Margolis & Joseph Schlessinger - 1993 - Bioessays 15 (3):179-183.
    The vav proto‐oncogene encodes a 95 kDa protein which is expressed exclusively in hematopoietic cells. Analysis of the deduced amino acid sequence has revealed the presence of a src‐homology 2 (SH2) domain, 2 SH3 domains, a cysteine‐rich region with similarity to protein kinase C, and a region highly similar to proteins with guanine nucleotide exchange activity on ras‐like GTPases. Recent work has shown that vav is tyrosine phosphorylated in response to stimulation of surface membrane receptors in a (...)
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  40.  7
    Phosphatidylinositol 3‐kinase.Rosana Kapeller & Lewis C. Cantley - 1994 - Bioessays 16 (8):565-576.
    Currently, a central question in biology is how signals from the cell surface modulate intracellular processes. In recent years phosphoinositides have been shown to play a key role in signal transduction. Two phosphoinositide pathways have been characterized, to date. In the canonical phosphoinositide turnover pathway, activation of phosphatidylinositol‐specific phospholipase C results in the hydrolysis of phosphatidylinositol 4,5‐bisphospate and the generation of two second messengers, inositol 1,4,5‐trisphosphate and diacylglycerol. The 3‐phosphoinositide pathway involves protein‐tyrosine kinase‐mediated recruitment and activation of phosphatidylinositol (...)
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  41.  20
    Pathways of human T lymphocyte development and activation.Andres Alcover, Claudio Milanese & Ellis L. Reinherz - 1986 - Bioessays 4 (6):259-264.
    The T lymphocyte receptor for antigen, which operates in conjunction with gene products of the major histocompatibility complex (MHC), is a molecular complex comprised of five polypeptide chains. Both the 49 kDa alpha and 43 kDa beta chains are immunoglobulin‐like and thus contain variable domains responsible for ligand binding. In contrast, the 20–25 kDa T3 gamma, delta and epsilon chains are monomorphic structures presumably involved in transmembrane signalling. The alpha and beta subunits are disulfide bonded to each other and held (...)
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  42.  30
    Tumour suppressors, kinases and clamps: How p53 regulates the cell cycle in response to DNA damage.Lynne S. Cox & David P. Lane - 1995 - Bioessays 17 (6):501-508.
    The human tumour suppressor protein p53 is critical for regulation of the cell cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral infection, cells respond rapidly by arresting the cell cycle. A G1 arrest requires the activity of wild‐type p53, as it is not observed in cells lacking functionally wild‐type protein, and at least some component of S phase and G2/M arrests is also thought to be p53‐dependent. p53 functions as a transcription factor which (...)
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  43.  33
    The Many Roles of Type II Phosphatidylinositol 4-Kinases in Membrane Trafficking: New Tricks for Old Dogs.Shane Minogue - 2018 - Bioessays 40 (2):1700145.
    The type II phosphatidylinositol 4-kinases produce the lipid phosphatidylinositol 4-phosphate and participate in a confusing variety of membrane trafficking and signaling roles. This review argues that both historical and contemporary evidence supports the function of the PI4KIIs in numerous trafficking pathways, and that the key to understanding the enzymatic regulation is through membrane interaction and the intrinsic membrane environment. By summarizing new research and examining the trafficking roles of the PI4KIIs in the context of recently solved molecular structures, I highlight (...)
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  44.  21
    The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species.C. I. Edvard Smith, Tahmina C. Islam, Pekka T. Mattsson, Abdalla J. Mohamed, Beston F. Nore & Mauno Vihinen - 2001 - Bioessays 23 (5):436-446.
    Cytoplasmic protein-tyrosine kinases (PTKs) are enzymes involved in transducing a vast number of signals in metazoans. The importance of the Tec family of kinases was immediately recognized when, in 1993, mutations in the gene encoding Bruton's tyrosine kinase (Btk) were reported to cause the human disease X-linked agammaglobulinemia (XLA).(1,2) Since then, additional kinases belonging to this family have been isolated, and the availability of full genome sequences allows identification of all members in selected species enabling phylogenetic considerations. Tec (...)
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  45.  9
    Conformational flexibility of β‐arrestins – How these scaffolding proteins guide and transform the functionality of GPCRs.Raphael S. Haider, Mona Reichel, Edda S. F. Matthees & Carsten Hoffmann - 2023 - Bioessays 45 (8).
    G protein‐coupled receptors (GPCRs) constitute the largest family of transmembrane proteins and play a crucial role in regulating diverse cellular functions. They transmit their signaling via binding to intracellular signal transducers and effectors, such as G proteins, GPCR kinases, and β‐arrestins. To influence specific GPCR signaling behaviors, β‐arrestins recruit effectors to form larger signaling complexes. Intriguingly, they facilitate divergent functions for the binding to different receptors. Recent studies relying on advanced structural approaches, novel biosensors and interactome analyses bring us (...)
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  46.  43
    A Link Between Alzheimer's and Type II Diabetes Mellitus? Ca+2 -Mediated Signal Control and Protein Localization.Yuko Tsutsui & Franklin A. Hays - 2018 - Bioessays 40 (6):1700219.
    We propose protein localization dependent signal activation (PLDSA) as a model to describe pre‐existing protein partitioning between the cytosol, and membrane surface, as a means to modulate signal activation, specificity, and robustness. We apply PLDSA to explain possible molecular links between type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) by describing Ca+2‐mediated interactions between the Src non‐receptor tyrosine kinase and p52Shc adaptor protein. We suggest that these interactions may serve as a contributing factor to disease (...)
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  47.  11
    Werner syndrome protein, the MRE11 complex and ATR: menage‐à‐trois in guarding genome stability during DNA replication?Pietro Pichierri & Annapaola Franchitto - 2004 - Bioessays 26 (3):306-313.
    The correct execution of the DNA replication process is crucially import for the maintenance of genome integrity of the cell. Several types of sources, both endogenous and exogenous, can give rise to DNA damage leading to the DNA replication fork arrest. The processes by which replication blockage is sensed by checkpoint sensors and how the pathway leading to resolution of stalled forks is activated are still not completely understood. However, recent emerging evidence suggests that one candidate for a sensor of (...)
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  48.  22
    The assembly of signalling complexes by receptor tyrosine kinases.George Panayotou & Michael D. Waterfield - 1993 - Bioessays 15 (3):171-177.
    Cell proliferation in response to growth factors is mediated by specific high affinity receptors. Ligand‐binding by receptors of the protein tyrosine kinase family results in the stimulation of several intracellular signal transduction pathways. Key signalling enzymes are recruited to the plasma membrane through the formation of stable complexes with activated receptors. These interactions are mediated by the conserved, non‐catalytic SH2 domains present in the signalling molecules, which bind with high affinity and specificity to tyrosine‐phosphorylated sequences on the receptors. (...)
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  49.  25
    Long-lasting potentiation of GABAergic inhibitory synaptic transmission in cerebellar Purkinje cells: Its properties and possible mechanisms.Masanobu Kano - 1996 - Behavioral and Brain Sciences 19 (3):354-361.
    The cellular basis of motor learning in the cerebellum has been attributed mostly to long-term depression (LTD) at excitatory parallel fiber (PF)-Purkinje cell (PC) synapses. LTD is induced when PFs are activated in conjunction with a climbing fiber (CF), the other excitatory input to PCs. Recently, by using whole-cell patch-clamp recording from PCs in cerebellar slices, a new form of synaptic plasticity was discovered. Stimulation of excitatory CFs induced a long-lasting (usually longer than 30 min) of 30 sec) and the (...)
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  50.  43
    Ethylene hormone receptor action in Arabidopsis.Caren Chang & Ruth Stadler - 2001 - Bioessays 23 (7):619-627.
    Small gaseous molecules play important roles in biological signaling in both animal and plant physiology. The hydrocarbon gas ethylene has long been known to regulate diverse aspects of plant growth and development, including fruit ripening, leaf senescence and flower abscission. Recent progress has been made toward identifying components involved in ethylene signal transduction in the plant Arabidopsis thaliana. Ethylene is perceived by five receptors that have similarity to two‐component signaling proteins. The hydrophobic amino‐terminus of the receptors binds ethylene, and mutations (...)
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