Human adenylate kinase 6 regulates WNK1 (with no lysine kinase-1) phosphorylation states and affects ion homeostasis in NT2 cells

Ke, Shengwei; Zhang, Ran; He, Yaohui; Mu, Huawei; Sun, Fei; Liu, Wen; Li, Jianyuan; Song, Xiaoyuan

doi:10.1016/j.yexcr.2021.112565

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…In addition, WNK1 is also found to act as a scaffolding protein to recruit SPAK/OSR1 on its target proteins, such as NBCs, and this effect is dependent on the phosphorylation of residue Ser-60 [ 70 ]. Interestingly, phosphorylation of WNK1 at residue Ser-60 in cancer cells is also found to support the catalytic function of WNK1, such as inducing phosphorylation of SPAK/OSR1 and CLC3 [ 50 , 74 , 75 ]. Since the phosphorylation of WNKs is the key to their subsequent function, it is necessary to clarify the relationship between different phosphorylation sites and the catalytic/scaffolding function of WNKs in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Through this mechanism, CLC3 is involved in cancer progression by controlling cancer cell shrinkage during invasion [ 49 ]. In human testicular cancer cells, the activity of volume-regulated chloride channel CLC3 is regulated by WNK1, which is activated by adenylate kinase 6 (AK6) [ 50 ] (Fig. 2 ).…”

Section: Wnks Modulate Ion Channels Cccs and Nbcs In Cancermentioning

confidence: 99%

“…Mechanistically, AK6 can directly bind to WNK1 protein and induce the phosphorylation of WNK1 on residue Thr-60. Knockdown of AK6 can decrease the expression of WNK1 and CLC3, resulting in increased intracellular Cl − concentration in cancer cells upon hypotonic conditions [ 50 ]. The dysregulation of CLC3-controlled RVD can inhibit cancer cell proliferation and induce cell apoptosis, indicating the critical role of the AK6-WNK1-CLC3 axis during cancer progression [ 50 ].…”

Section: Wnks Modulate Ion Channels Cccs and Nbcs In Cancermentioning

confidence: 99%

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An update regarding the role of WNK kinases in cancer

Xiu

et al. 2022

Cell Death Dis

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Mammalian WNK kinases (WNKs) are serine/threonine kinases that contain four members, WNK1–4. They function to maintain ion homeostasis and regulate blood pressure in mammals. Recent studies have revealed that the dysregulation of WNKs contributes to tumor growth, metastasis, and angiogenesis through complex mechanisms, especially through phosphorylating kinase substrates SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1). Here, we review and discuss the relationships between WNKs and several key factors/biological processes in cancer, including ion channels, cation chloride cotransporters, sodium bicarbonate cotransporters, signaling pathways, angiogenesis, autophagy, and non-coding RNAs. In addition, the potential drugs for targeting WNK-SPAK/OSR1 signaling have also been discussed. This review summarizes and discusses knowledge of the roles of WNKs in cancer, which provides a comprehensive reference for future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Wnks Modulate Ion Channels Cccs and Nbcs In Cancermentioning

confidence: 99%

Section: Wnks Modulate Ion Channels Cccs and Nbcs In Cancermentioning

confidence: 99%

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An update regarding the role of WNK kinases in cancer

Xiu

et al. 2022

Cell Death Dis

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Aberrant expression of WNK lysine deficient protein kinase 1 is associated with poor prognosis of colon adenocarcinoma

et al. 2022

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Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells

et al. 2022

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Changes in dynamics of ATP γ- and β-phosphoryl turnover and metabolic flux through phosphotransfer pathways in cancer cells are still unknown. Using 18O phosphometabolite tagging technology, we have discovered phosphotransfer dynamics in three breast cancer cell lines: MCF7 (non-aggressive), MDA-MB-231 (aggressive), and MCF10A (control). Contrary to high intracellular ATP levels, the 18O labeling method revealed a decreased γ- and β-ATP turnover in both breast cancer cells, compared to control. Lower β-ATP[18O] turnover indicates decreased adenylate kinase (AK) flux. Aggressive cancer cells had also reduced fluxes through hexokinase (HK) G-6-P[18O], creatine kinase (CK) [CrP[18O], and mitochondrial G-3-P[18O] substrate shuttle. Decreased CK metabolic flux was linked to the downregulation of mitochondrial MTCK1A in breast cancer cells. Despite the decreased overall phosphoryl flux, overexpression of HK2, AK2, and AK6 isoforms within cell compartments could promote aggressive breast cancer growth.

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Human adenylate kinase 6 regulates WNK1 (with no lysine kinase-1) phosphorylation states and affects ion homeostasis in NT2 cells

Cited by 3 publications

References 31 publications

An update regarding the role of WNK kinases in cancer

An update regarding the role of WNK kinases in cancer

Aberrant expression of WNK lysine deficient protein kinase 1 is associated with poor prognosis of colon adenocarcinoma

Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells

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