(WNK)ing at death: With-no-lysine (Wnk) kinases in neuropathies and neuronal survival

Tang, Bor Luen

doi:10.1016/j.brainresbull.2016.04.017

Cited by 16 publications

(13 citation statements)

References 123 publications

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“…It has been proposed that the site normally occupied by the β3 lysine functions as a chloride sensor by binding to halide ions and inhibiting WNK activation by autophosphorylation, thus facilitating a feedback mechanism for the regulation of Cllevels [98]. Consistently, in its active state, WNKs phosphorylate and activate SPAK and the oxidative stress response kinase (OSR1), which in turn modulate the downstream activities of Na+-driven, Cl --importing NKCCs (Na+/K+/Clcotransporters) in order to modulate blood pressure and ion homeostasis [97].…”

Section: Wnkmentioning

confidence: 99%

“…The WNK family of Ser/Thr pseudokinases (comprising WNK1-4) [97] are defined because they lack the conserved β3 lysine, which was long assumed to be indispensable for nucleotide binding and stabilization of the active kinase conformation [26]. Despite this apparent handicap, WNK family kinases readily demonstrate phosphorylation-dependent regulation of a host of intracellular substrates.…”

Section: Wnkmentioning

confidence: 99%

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Pseudokinases: Update on Their Functions and Evaluation as New Drug Targets

2017

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The pseudokinase complement of the human kinase superfamily consists of approximately 60 signaling proteins, which lacks one or more of the amino acids typically required to correctly align ATP and metal ions, and phosphorylate protein substrates. Recent studies in the pseudokinase field have begun to expose the biological relevance of pseudokinases, which are now thought to perform a diverse range of physiological roles and are connected to a multitude of human diseases, including cancer. In this review, we discuss how and why members of the 'pseudokinome' represent important new targets for drug discovery, and describe how knowledge of protein structure and function provides informative clues to help guide the rational chemical design or repurposing of inhibitors to target pseudokinases.

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Section: Wnkmentioning

confidence: 99%

Section: Wnkmentioning

confidence: 99%

Pseudokinases: Update on Their Functions and Evaluation as New Drug Targets

2017

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“…One possible mechanism is through activation of WNK1 by intracellular taurine, which is high in the fetal brain, though additional mechanisms may also play a role (Inoue et al, 2012). Additional roles for WNK signaling in nervous system physiology and disease are reviewed in (Alessi et al, 2014) and (Tang, 2016). …”

Section: Emerging Functions Of the Wnk Signaling Axis In Developmentmentioning

confidence: 99%

“…WNK kinases have been linked to various cancers in recent years, although the mechanism by which they act is not well understood (for reviews see also (McCormick and Ellison, 2011; Moniz and Jordan, 2010; Tang, 2016)). Since WNKs can positively regulate Wnt signaling in Drosophila and cultured human cells, it is conceivable that WNKs affect Wnt related cancers such as the ones of the colon that are frequently caused by increased Wnt signaling (Clevers and Nusse, 2012).…”

Section: Functions Of Wnks In Cancermentioning

confidence: 99%

WNK Kinases in Development and Disease

Rodan

Jenny

2017

Current Topics in Developmental Biology

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WNK (With-No-Lysine (K)) kinases are serine-threonine kinases characterized by an atypical placement of a catalytic lysine within the kinase domain. Mutations in human WNK1 or WNK4 cause an autosomal dominant syndrome of hypertension and hyperkalemia, reflecting the fact that WNK kinases are critical regulators of renal ion transport processes. Here, the role of WNKs in the regulation of ion transport processes in vertebrate and invertebrate renal function, cellular and organismal osmoregulation, cell migration and cerebral edema will be reviewed, along with emerging literature demonstrating roles for WNKs in cardiovascular and neural development, Wnt signaling, and cancer. Conserved roles for these kinases across phyla are emphasized.

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“…В частности, различные изофор-мы WNK в клетках центральной нервной системы подавляют развитие опухолей, препятствуют ише-мическому повреждению нейронов головного мозга и их апоптозу; мутации в генах WNK сопровожда-ются развитием целого ряда неврологических забо-леваний [34]. Можно предположить, что не только нефротоксическое, но и побочное действие на цент-ральную нервную систему ингибиторов кальцинев-рина может объясняться их подавляющим действи-ем на систему киназ WNK.…”

Section: ингибиторы кальциневринаunclassified

Hypertension in cardiac transplant recipients

Шевченко

Никитина

Тюняева

2017

RJTAO

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1 ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва, Российская Федерация 2 ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский университет), Москва, Российская ФедерацияАртериальная гипертония -один из наиболее распространенных патологических синдромов среди реци-пиентов трансплантированноого сердца, как взрослых, так и детей. Хроническое повышение артериаль-ного давления является важным модифицируемым фактором риска дисфункции сердечного трансплан-тата, васкулопатии, жизнеопасных нарушений ритма, мозгового инсульта, почечной недостаточности и смерти. Данная статья построена на обзоре литературы и посвящена особенностям патогенеза, профи-лактики, немедикаментозной и лекарственной терапии посттрансплантационной артериальной гиперто-нии у реципиентов сердца.Ключевые слова: трансплантация сердца, реципиент сердца, артериальная гипертония, профилактика, лечение.

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(WNK)ing at death: With-no-lysine (Wnk) kinases in neuropathies and neuronal survival

Cited by 16 publications

References 123 publications

Pseudokinases: Update on Their Functions and Evaluation as New Drug Targets

Pseudokinases: Update on Their Functions and Evaluation as New Drug Targets

WNK Kinases in Development and Disease

Hypertension in cardiac transplant recipients

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