Abstract:
:JAK2 is a member of the Janus kinase (JAKs) family of non-receptor protein tyrosine kinases, which includes JAK1-3 and TYK2. JAKs serve as the cytoplasmic signaling components of cytokine receptors and are activated through cytokine-mediated trans-phosphorylation, which leads to receptor phosphorylation and recruitment and phosphorylation of signal transducer and activator of transcription (STAT) proteins. JAKs are unique among tyrosine kinases in that they possess a pseudokinase domain, which is just upstream of the C-terminal tyrosine kinase domain. A wealth of biochemical and clinical data have established that the pseudokinase domain of JAKs is crucial for maintaining a low basal (absence of cytokine) level of tyrosine kinase activity. In particular, gain-of-function mutations in the JAK genes, most frequently, V617F in the pseudokinase domain of JAK2, have been mapped in patients with blood disorders, including myeloproliferative neoplasms and leukemias. Recent structural and biochemical studies have begun to decipher the molecular mechanisms that maintain the basal, low-activity state of JAKs and that, via mutation, lead to constitutive activity and disease. This review will examine these mechanisms and describe how this knowledge could potentially inform drug development efforts aimed at obtaining a mutant (V617F)-selective inhibitor of JAK2.
journal_name
Front Endocrinol (Lausanne)journal_title
Frontiers in endocrinologyauthors
Hubbard SRdoi
10.3389/fendo.2017.00361subject
Has Abstractpub_date
2018-01-05 00:00:00pages
361issn
1664-2392journal_volume
8pub_type
杂志文章,评审abstract::Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well established for several tumor types, such as breast cancer in post-menopausal women, colorectal, and prostate ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2014.00065
更新日期:2014-05-01 00:00:00
abstract::Gonadotropin-releasing hormone (GnRH) is the ultimate output signal of an intricate network of neuroendocrine factors that, acting on the pituitary, trigger gonadotropin release. In turn, gonadotropins exert their trophic action on the gonads to stimulate the synthesis of sex steroids thus completing the gonadotropic ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2012.00048
更新日期:2012-04-02 00:00:00
abstract::Background: The effect of testosterone supplementation in patients with chronic heart failure (CHF) remains uncertain. Methods: A meta-analysis of randomized controlled trials (RCTs) was performed. RCTs that evaluate the chronic effect of testosterone supplementation on exercise capacity and cardiac function in CHF we...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,meta分析
doi:10.3389/fendo.2020.00110
更新日期:2020-03-13 00:00:00
abstract::Autophagy requires the conjugation of autophagy-related protein 12 (ATG12) to autophagy-related protein 5 (ATG5) through covalent attachment. However, the signals regulating ATG12-ATG5 conjugation are unclear. The larval midgut of lepidopteran insects performs autophagy and apoptosis sequentially during the transition...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00028
更新日期:2018-02-07 00:00:00
abstract::This brief review describes some representative methodological approaches to the isolation of putative endogenous inhibitors of epithelial sodium transport - i.e., as ouabain-like factors (OLF) that inhibit the sodium transport enzyme Na-K-ATPase or inhibit the epithelial sodium channel (ENaC). Gel chromatography and ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00066
更新日期:2015-05-20 00:00:00
abstract::Progression and severity of type 1 diabetes is dependent upon inflammatory induction of nitric oxide production and consequent pancreatic β-cell damage. Glucocorticoids (GCs) are highly effective anti-inflammatory agents but have been precluded in type 1 diabetes and in islet transplantation protocols because they exa...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2014.00165
更新日期:2014-10-14 00:00:00
abstract::Poor sleep and obesity are both extraordinarily common in the US adolescent population and often occur simultaneously. This review explores the links between obesity and sleep, outlining what is known about the relationships between sleep characteristics, obesity, and cardiometabolic risk factors in youth. Sleep durat...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00364
更新日期:2018-07-10 00:00:00
abstract::Background: Consistent evidence have demonstrated that patients with primary aldosteronism (PA) have higher risk of cardiovascular events to patients with essential hypertension (EH). Whether the long-term risk of mortality for PA patients is higher than EH patients is unclear. We aim to compare the long-term mortalit...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00121
更新日期:2020-03-10 00:00:00
abstract::Background: Several preclinical and clinical studies have suggested that BRCA-mutation carriers may have decreased ovarian reserve. However, data in this area are limited and inconsistent, especially in young breast cancer patients. Objective: This study evaluated the association between BRCA mutation status and serum...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00235
更新日期:2019-04-11 00:00:00
abstract::Background: Disturbance of immunometabolic signaling is a key process involved in the progression of obesity. Microglia-the resident immune cells in the brain, initiate local immune responses. It is known that hypercaloric diets lead to microglial activation. Previously, we observed that hypothalamic microglial cells ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00424
更新日期:2019-06-26 00:00:00
abstract::Background: The number of subjects with gender dysphoria has been increasing. In general, male-to-female transsexual subjects are treated with estradiol valerate therapy. In this report, we showed the time course of ACTH and cortisol levels after estradiol valerate injection in a male subject with gender dysphoria. It...
journal_title:Frontiers in endocrinology
pub_type:
doi:10.3389/fendo.2019.00751
更新日期:2019-11-05 00:00:00
abstract:Objective:Both vitamin D and K2 are involved in a number of metabolic processes, including bone metabolism; however, associations between the vitamins are not fully understood. The aim of the study was to evaluate serum concentrations of 25-hydroxyvitamin D [25(OH)D] in adult patients receiving long-term acenocoumarol ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00226
更新日期:2018-05-04 00:00:00
abstract::Estetrol (E4) is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor (ER) modulator, exerting estrogenic actions on the endometrium or...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2014.00080
更新日期:2014-05-26 00:00:00
abstract::Co-heritability of hypertension and insulin resistance (IR) within families not only implies genetic susceptibility may be responsible for these complex traits but also suggests a rational that biological candidate genes for hypertension may serve as markers for features of the metabolic syndrome (MetS). Thus we deter...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00172
更新日期:2013-11-28 00:00:00
abstract::A direct action of thyrotropin (TSH, thyroid-stimulating hormone) on bone precursors in humans is controversial. Studies in rodent models have provided conflicting findings. We used cells derived from a moderately differentiated osteosarcoma stably overexpressing human TSH receptors (TSHRs) as a model of osteoblast pr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00312
更新日期:2020-05-20 00:00:00
abstract:Objective:Individuals with diabetic peripheral neuropathy (DPN) have functional deficits that increase their risk of falling. However, psychological aspects such as loss of confidence in undertaking activities could also contribute to this risk. We examined correlations between balance confidence and fall risk among in...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.573804
更新日期:2020-10-23 00:00:00
abstract::Osteoporosis is a metabolic skeletal disorder in which bone mass is depleted and bone structure is destroyed to the degree that bone becomes fragile and prone to fractures. Emerging evidence suggests that N6-methyladenosine (m6A) modification, a novel epitranscriptomic marker, has a significant role in bone developmen...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00911
更新日期:2020-01-10 00:00:00
abstract::Background: Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. As a leading cause of anovulatory infertility, the molecular diversity of the follicular microenvironment has not been fully elucidated. The aim of the present study was to i...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00821
更新日期:2019-11-26 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV)/AIDS pandemic represents the most significant global health challenge in modern history. This infection leads toward an inflammatory state associated with chronic immune dysregulation activation that tilts the immune-skeletal interface and its deep integration between cell...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00502
更新日期:2020-09-02 00:00:00
abstract::The origin of the coronavirus disease 2019 (COVID-19) pandemic is zoonotic. The circadian day-night is the rhythmic clue to organisms for their synchronized body functions. The "development for mankind" escalated the use of artificial light at night (ALAN). In this article, we tried to focus on the possible influence ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00622
更新日期:2020-09-10 00:00:00
abstract::In some organisms and cells, oxygen availability influences oxygen consumption. In this review, we examine this phenomenon of hypoxic hypometabolism (HH), discussing its features, mechanisms, and implications. Small mammals and other vertebrate species exhibit "oxyconformism," a downregulation of metabolic rate and bo...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00668
更新日期:2018-11-13 00:00:00
abstract:Background:The association between normal range thyroid function and offspring birth weight has been postulated, but evidence from observational studies is prone to be confounded. We conducted a two-sample Mendelian randomization (MR) study to explore the causal effects of maternal thyroid stimulating hormone (TSH) and...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.601956
更新日期:2020-11-12 00:00:00
abstract::There is increasing evidence supporting the characterization of the pesticide DDT and its metabolite, DDE, as obesogens and metabolic disruptors. Elucidating the mechanism is critical to understanding whether the association of DDT and DDE with obesity and diabetes is in fact causal. One area of research investigating...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00122
更新日期:2019-03-12 00:00:00
abstract::The islet amyloid polypeptide (IAPP) or amylin maintains a key role in metabolism. This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. However, some species do not form amyloid fibril structures. By employing a biomimetic approach, we generated an ex...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00331
更新日期:2018-06-25 00:00:00
abstract::Linagliptin, one of the five dipeptidyl peptidase-4 inhibitors available, has recently entered the market both in the US and in most European countries for treatment of type 2 diabetes mellitus. It presents a xanthine-based structure, and is characterized by unique pharmacokinetics, with non-linear profile, long termi...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00016
更新日期:2013-02-26 00:00:00
abstract::Accumulating evidence shows that H2S has physiological functions in various tissues and organs. It includes regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H2S is produced by enzymes from l-cysteine; cystathionine β-synthase,...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00087
更新日期:2013-07-16 00:00:00
abstract::Anaplastic thyroid cancer is known to be the most lethal malignancy among endocrine tumors for its extremely limited survival rate after diagnosis. As a result of this poor survival prognosis, multimodal therapy is currently under investigation to address this global concern. In this reported case, the 125I seed impla...
journal_title:Frontiers in endocrinology
pub_type:
doi:10.3389/fendo.2020.00207
更新日期:2020-04-22 00:00:00
abstract::We sought to determine the efficacy of 12 weeks high-intensity interval training (HIIT), compared to moderate-intensity continuous training (MICT) on glucose control, cardiometabolic risk and microvascular complication markers in men living with type 2 diabetes (T2D). Both modalities were combined with resistance trai...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00475
更新日期:2018-08-28 00:00:00
abstract::Congenital hypogonadotrophic hypogonadism (CHH) is a rare but important etiology of pubertal failure and infertility, resulting from impaired gonadotrophin-releasing hormone secretion or action. Despite the availability of effective hormonal therapies, the majority of men with CHH experience unsatisfactory outcomes, i...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00097
更新日期:2019-02-21 00:00:00
abstract::Bone marrow adipose tissue (MAT) is distinct from white adipose tissue (WAT) or brown adipose tissue (BAT) for its location, feature and function. As a largely ignored adipose depot, it is situated in bone marrow space and resided with bone tissue side-by-side. MAT is considered not only as a regulator of bone metabol...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00069
更新日期:2019-02-08 00:00:00