Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway

Verı́ssimo, Fátima; Silva, E; Morris, Jeremy; Pepperkok, Rainer; Jordan, Peter

doi:10.1038/sj.onc.1209449

Cited by 39 publications

(40 citation statements)

References 57 publications

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“…WNKs have been proposed to have many functions besides the modulation of electroneutral cation-coupled chloride cotransporters, including regulating basic cellular processes such as mitosis (25), apoptosis (27) and neoplastic transformation (19), regulating synaptagmin 2 (15), and interacting with many other kinases, like TGF-␤ (14), MAP kinases (31), and the STE20-related alanine/proline-rich kinases SPAK and OSR1 (28) (for an excellent review, see Ref. 16).…”

Section: Effects Of the Catalytically Inactive Wnk3 Variants On The Cmentioning

confidence: 99%

Similar effects of all WNK3 variants on SLC12 cotransporters

Cruz-Rangel

Melo

Vázquez

et al. 2011

American Journal of Physiology-Cell Physiology

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kinase 3 (WNK3) is a member of a subfamily of serine/threonine kinases that modulate the activity of the electroneutral cation-coupled chloride cotransporters. WNK3 activates NKCC1/2 and NCC and inhibits the KCCs. Four splice variants are generated from the WNK3 gene. Our previous studies focused on the WNK3-18a variant. However, it has been suggested that other variants could have different effects on the cotransporters. Thus, the present study was designed to define the effects of all WNK3 variants on members of the SLC12 family. By RT-PCR from a fetal brain library, exons 18b and 22 were separately amplified and subcloned into the original WNK3-18a or catalytically inactive WNK3-D294A to obtain all four potential combinations with and without catalytic activity (18a, 18aϩ22, 18b, and 18bϩ22). The basal activity of the cotransporters and the effects of WNK3 isoforms were assessed in Xenopus laevis oocytes coinjected with each of the WNK3 variant cRNAs. In isotonic conditions, the basal activity of NCC and NKCC1/2 were increased by coinjection with any of the WNK3. The positive effects occurred even in hypotonic conditions, in which the basal activity of NKCC1 is completely prevented. Consistent with these observations, when expressed in hypotonicity, all KCCs were active, but in the presence of any of the WNK3 variants, KCC activity was completely reduced. That is, NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions. We conclude that the effects of all WNK3 variants toward SLC12 proteins are similar.

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Section: Effects Of the Catalytically Inactive Wnk3 Variants On The Cmentioning

confidence: 99%

Similar effects of all WNK3 variants on SLC12 cotransporters

Cruz-Rangel

Melo

Vázquez

et al. 2011

American Journal of Physiology-Cell Physiology

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“…ERK5 is implicated in proliferative as well as developmental pathways, notably in cardiovascular development (Nicol et al, 2001;Yan et al, 2003). WNK3 pro-motes cell survival by inhibiting caspase-3 (Verissimo et al, 2006). In addition, WNKs modulate TGFβ-Smad signaling (Lee et al, 2007).…”

Section: Role Of Wnk Kinases In Cell Signaling Proliferation Survivmentioning

confidence: 99%

WNKs: protein kinases with a unique kinase domain

Huang

Kuy²,

Wang³

et al. 2007

Exp Mol Med

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WNKs (with-no-lysine [K]) are a family of serine-threonine protein kinases with an atypical placement of the catalytic lysine relative to all other protein kinases. The roles of WNK kinases in regulating ion transport were first revealed by the findings that mutations of two members cause a genetic hypertension and hyperkalemia syndrome. More recent studies suggest that WNKs are pleiotropic protein kinases with important roles in many cell processes in addition to ion transport. Here, we review roles of WNK kinases in the regulation of ion balance, cell signaling, survival, and proliferation, and embryonic organ development.

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“…However, neither knockdown nor overexpression of WNK1 had any effect on neuronal survival, indicating that WNK1 is not involved in the regulation of neuronal apoptosis (5). Among the four known WNK family members, only WNK3 has been reported to regulate cell survival (17). In this study, we found that WNK3 had a potent prosurvival effect on serum-deprived cortical neurons.…”

Section: Discussionmentioning

confidence: 54%

“…To further assess the role of WNK3 kinase activity in neuronal apoptosis, we expressed a transgenic form of WNK3 containing the entire catalytic domain, WNK(49 -436) (27), or a kinase-dead mutant form of the same transgene, WNK3(49 -436)K159M (17). Both constructs were cloned into pEGFP-N1 and transfected into cultured cortical neurons.…”

Section: Effect Of Lingo-1 On Neuronalmentioning

confidence: 99%

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LINGO-1 Receptor Promotes Neuronal Apoptosis by Inhibiting WNK3 Kinase Activity

Zhang

Xiang

et al. 2013

Journal of Biological Chemistry

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Background: Although antagonism of LINGO-1 is known to improve neuronal survival after injury, the mechanism is unknown. Results: LINGO-1 interacts with and inhibits WNK3 kinase activity, thereby facilitating neuronal apoptosis. Conclusion: LINGO-1 potentiates neuronal apoptosis, likely by inhibiting WNK3 kinase activity. Significance: Learning how LINGO-1/WNK3 signaling regulates neuronal survival is crucial for understanding the pathology of neurodegenerative diseases and injury.

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Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway

Cited by 39 publications

References 57 publications

Similar effects of all WNK3 variants on SLC12 cotransporters

Similar effects of all WNK3 variants on SLC12 cotransporters

WNKs: protein kinases with a unique kinase domain

LINGO-1 Receptor Promotes Neuronal Apoptosis by Inhibiting WNK3 Kinase Activity

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