Abstract:
:It is now generally accepted that protein phosphorylation-dephosphorylation has a role in the regulation of essentially all cellular functions. Thus, it is of interest that this process is involved in signal transduction. Nonetheless, the extent to which protein phosphorylation participates in signaling is truly remarkable. Almost every known signaling pathway eventually impinges on a protein kinase, or in some instances, a protein phosphatase. The diversity of these enzymes is noteworthy, and it is of interest that many biotechnology companies are eyeing them as potentially important targets for drugs. Such drugs may have important therapeutic applications, and in any event, they certainly will be useful to investigators who study signal transduction. Indeed, this already has been proven to be true.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Graves JD,Krebs EGdoi
10.1016/s0163-7258(98)00056-4subject
Has Abstractpub_date
1999-05-01 00:00:00pages
111-21issue
2-3eissn
0163-7258issn
1879-016Xjournal_volume
82pub_type
杂志文章,评审abstract::Common arrhythmias, particularly atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are a major public health concern. Classic antiarrhythmic (AA) drugs for AF are of limited effectiveness, and pose the risk of life-threatening VT/VF. For VT/VF, implantable cardiac defibrillators appear to be th...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2011.03.003
更新日期:2011-11-01 00:00:00
abstract::There is substantial molecular evidence for the involvement of beta1 integrin in tissue organisation and remodelling, which confers a key role in cell growth, differentiation, migration, and survival. This role has been, in part, highlighted using the transgenic approach which does little to define the more subtle fun...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.07.002
更新日期:2008-11-01 00:00:00
abstract::The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(98)00013-8
更新日期:1998-08-01 00:00:00
abstract::Recent epidemiologic studies have shown that aerobic exercise, one of lifestyle modifications, reduces cardiovascular morbidity and mortality in the general population. However, the mechanisms underlying the anti-atherogenic and anti-hypertensive effects of exercise remain unclear. Hypertension is associated with alte...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2004.02.003
更新日期:2004-04-01 00:00:00
abstract::Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tis...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(97)00021-1
更新日期:1997-01-01 00:00:00
abstract::The aromatic amine 2-acetylaminofluorene (AAF) produced neoplasms in diverse target organs of many animal species. AAF was DNA-reactive after N-hydroxylation by CYP1A2 in the liver and nitrenium ion formation at the target site. In mouse bladder, AAF-DNA adducts were proportional to dose. An epigenetic component for t...
journal_title:Pharmacology & therapeutics
pub_type: 共识发展会议,杂志文章,评审
doi:10.1016/0163-7258(96)00063-0
更新日期:1996-01-01 00:00:00
abstract::Although the interaction between FUra and DP in HCT 116 cells is fairly complex, data from other investigators indicate that in cell lines in which inhibition of TS is growth limiting at relatively low concentrations of fluoropyrimidines, DP appears to augment the cytotoxicity of FUra and FdUrd by blocking the salvage...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(89)90084-3
更新日期:1989-01-01 00:00:00
abstract::The understanding of renal fibrosis in chronic kidney disease (CKD) remains as a challenge. More than 10% of the population of developed countries suffer from CKD. Proliferation and activation of myofibroblasts and accumulation of extracellular matrix proteins are the main features of kidney fibrosis, a process in whi...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2015.10.003
更新日期:2015-12-01 00:00:00
abstract::A variety of drug transporters expressed in the body control the fate of drugs by affecting absorption, distribution, and elimination processes. In the small intestine, transporters mediate the influx and efflux of endogenous or exogenous substances. In clinical pharmacotherapy, ATP-dependent efflux transporters (ATP-...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.06.005
更新日期:2006-01-01 00:00:00
abstract::Natural D-nucleosides are no longer the sole basis for designing effective antiviral analogues. Many antivirals with an opposite (L) configuration were reported, with lamivudine being the most notable example. In contrast, carbocyclic nucleoside analogues are significantly more enantioselective, and enantiomers with a...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(99)00062-5
更新日期:2000-03-01 00:00:00
abstract::New techniques for the analysis of proteins with specific binding for natural retinoids in human plasma and skin extracts have been developed. Polyacrylamide gel electrophoresis (PAGE), followed by protein blotting with an antiserum specific to retinol-binding protein (RBP), the plasma carrier of retinol, showed that:...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(89)90073-9
更新日期:1989-01-01 00:00:00
abstract::Evidence that the delta opioid receptor (DOR) is an attractive target for the treatment of brain disorders has strengthened in recent years. This receptor is broadly expressed in the brain, binds endogenous opioid peptides, and shows as functional profile highly distinct from those of mu and kappa opioid receptors. Ou...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2013.06.003
更新日期:2013-10-01 00:00:00
abstract::Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the va...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(92)90055-5
更新日期:1992-01-01 00:00:00
abstract::The demonstration that RNA can be cleaved by cis or trans ribozymes (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Since their discovery in the 1980s, the biochemistry and conserved sequences of ribozymes have been well characterized. Ribozymes are effective modulators of gene expres...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(95)02008-x
更新日期:1995-01-01 00:00:00
abstract::Unwanted cells are removed by physiological cell death processes that are highly conserved throughout the animal kingdom. Physiological cell death plays an important role in development, tissue homeostasis and defence against viral infection and mutation. This review describes the molecular components that implement t...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(96)00098-8
更新日期:1996-01-01 00:00:00
abstract::In the last decade, there have been considerable advances in the understanding of the pathophysiology of malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Over 80% of SCD occurs in patients with organic heart disease. However, approximately 10%-15% of SCD occurs in the presence of structurall...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2015.09.002
更新日期:2015-11-01 00:00:00
abstract::Arterial obstructive syndromes result in heart disease, stroke and limb loss, disability, and mortality. Currently available therapeutics for patients with these conditions are inadequate or fail in a significant number of patients. The development of novel therapies for severe coronary arterial disease (CAD), periphe...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.08.005
更新日期:2006-01-01 00:00:00
abstract::Canonical Wnt signaling is a highly conserved pathway with a prominent role in embryogenic development, adult tissue homeostasis, cell polarization, stem cell biology, cell differentiation, and proliferation. Furthermore, canonical Wnt signaling is of pivotal importance in the pathogenesis of a number of cancer types ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2015.11.001
更新日期:2016-01-01 00:00:00
abstract::Aquaporin (AQP) water and solute channels have basic physiological functions throughout the human body. AQP-facilitated water permeability across cell membranes is required for rapid reabsorption of water from pre-urine in the kidneys and for sustained near isosmolar water fluxes e.g. in the brain, eyes, inner ear, an...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2015.08.002
更新日期:2015-11-01 00:00:00
abstract::The vascular system develops during embryonic development by at least two distinct processes; vasculogenesis is the development of blood vessels from in situ differentiating angioblasts and angiogenesis is the sprouting of capillaries from pre-existing vessels. The molecular mechanisms involved in the regulation of th...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(91)90066-u
更新日期:1991-01-01 00:00:00
abstract::Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alt...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.03.006
更新日期:2016-05-01 00:00:00
abstract::Since the first reports on chemokine function, much information has been generated on the implications of these molecules in numerous physiological and pathological processes, as well as on the signaling events activated through their binding to receptors. Despite these extensive studies, no chemokine-related drugs ha...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2011.05.002
更新日期:2011-09-01 00:00:00
abstract::The RNA-dependent P1/eIF-2 alpha protein kinase is a highly specific protein-serine/threonine kinase that catalyzes the phosphorylation of the alpha subunit of protein synthesis initiation factor eIF-2. The kinase plays a central role in translational control. The activity of the kinase is regulated by a variety of na...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(92)90005-k
更新日期:1992-01-01 00:00:00
abstract::The receptor tyrosine kinase MERTK is aberrantly expressed in numerous human malignancies, and is a novel target in cancer therapeutics. Physiologic roles of MERTK include regulation of tissue homeostasis and repair, innate immune control, and platelet aggregation. However, aberrant expression in a wide range of liqui...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107577
更新日期:2020-09-01 00:00:00
abstract::AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor trafficking is a fundamental mechanism for regulating synaptic strength, and hence may underlie cellular processes involved in learning and memory. PICK1 (protein interacting with C-kinase) is a PDZ and BAR domain-containing protein that has rece...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.02.002
更新日期:2008-04-01 00:00:00
abstract::The receptors involved in bitter taste perception (bitter taste receptors--T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tis...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2015.08.001
更新日期:2015-11-01 00:00:00
abstract::Activation of receptors coupled to inhibitory G proteins (Galpha i/o) has opposing consequences for cyclic AMP accumulation and the activity of cyclic AMP-dependent protein kinase, depending on the duration of stimulation. Acute activation inhibits the activity of adenylate cyclase, thereby attenuating cyclic AMP accu...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2004.12.005
更新日期:2005-06-01 00:00:00
abstract::Stroke is a major clinical problem, and acute pharmacological intervention with neuroprotective agents has so far been unsuccessful. Recently, there has been considerable interest in the potential therapeutic benefit of nitrone-derived free radical trapping agents as neuroprotective agents. Nitrone compounds have been...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2003.07.003
更新日期:2003-12-01 00:00:00
abstract::Three separate experimental approaches, using site-selective cAMP analogs, antisense strategy and retroviral vector-mediated gene transfer, have provided evidence that two isoforms, the RI- and RII-regulatory subunits of cAMP-dependent protein kinase, have opposite roles in cell growth and differentiation; RI being gr...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(93)90010-b
更新日期:1993-11-01 00:00:00
abstract::Hyperkinetic movement disorders comprise a variety of conditions characterized by involuntary movements, which include but are not limited to tardive dyskinesia, chorea associated with Huntington's Disease, and tic disorders. The class of medications that have been used to treat these conditions includes Vesicular Mon...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107580
更新日期:2020-08-01 00:00:00