C -terminal phosphorylation of SPAK and OSR1 kinases promotes their binding and activation by the scaffolding protein MO25

Mehellou, Youcef ORCID: https://orcid.org/0000-0001-5720-8513, Alamri, Mubarak A., Dhiani, Binar A. and Kadri, Hachemi 2018. C -terminal phosphorylation of SPAK and OSR1 kinases promotes their binding and activation by the scaffolding protein MO25. Biochemical and Biophysical Research Communications 503 (3) , pp. 1868-1873. 10.1016/j.bbrc.2018.07.128

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Abstract

SPAK and OSR1 are two protein kinases that play important roles in regulating the function of numerous ion co-transporters. They are activated by two distinct mechanisms that involve initial phosphorylation at their T-loops by WNK kinases and subsequent binding to a scaffolding protein termed MO25. To understand this latter SPAK and OSR1 regulation mechanism, we herein show that MO25 binding to these two kinases is enhanced by serine phosphorylation in their highly conserved WEWS motif, which is located in their C-terminal domains. Furthermore, we show that this C-terminal phosphorylation is carried out by WNK kinases in vitro and involves WNK kinases in cells. Mutagenesis studies revealed key MO25 residues that are important for MO25 binding and activation of SPAK and OSR1 kinases. Collectively, this study provides new insights into the MO25-mediated activation of SPAK and OSR1 kinases, which are emerging as important players in regulating ion homeostasis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	0006-291X
Date of First Compliant Deposit:	30 July 2018
Date of Acceptance:	24 July 2018
Last Modified:	25 Nov 2024 15:30
URI:	https://orca.cardiff.ac.uk/id/eprint/113719

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