1 H, 15 N and 13 C resonance assignments of the HR1c domain of PRK1, a protein kinase C-related kinase
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ARTICLE
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H, 15N and 13C resonance assignments of the HR1c domain of PRK1, a protein kinase C-related kinase Georgios Sophocleous1 · George Wood1,2 · Darerca Owen1 · Helen R. Mott1 Received: 26 March 2020 / Accepted: 29 May 2020 © The Author(s) 2020
Abstract PRK1 is a member of the protein kinase C-related kinase (PRK) family of serine/threonine kinases and a downstream effector of Rho GTPases. PRK1 has three N-terminal Homology Region 1 (HR1) domains (HR1a, HR1b and HR1c), which form antiparallel coiled coils that interact with Rho family GTPases. PRK1 also has a C2-like domain that targets it to the plasma membrane and a kinase domain, which is a member of the protein kinase C superfamily. PRK1 is involved in cytoskeletal regulation, cell adhesion, cell cycle progression and the immune response, and is implicated in cancer. There is currently no structural information for the HR1c domain. The 1H, 15N and 13C NMR backbone and sidechain resonance assignment of the HR1c domain presented here forms the basis for this domain’s structural characterisation. This work will also enable studies of interactions between the three HR1 domains in an effort to obtain structural insight into the regulation of PRK1 activity. Keywords Small GTPase · Protein Kinase C related kinase · PKN · HR1 domain · Coiled-coil
Biological context Protein kinase C-related kinase 1 (PRK1) is a member of the PRK family of serine/threonine kinases, which is within the AGC group of kinases. The PRK proteins were first identified as effector kinases of the small G protein RhoA (Watanabe et al. 1996; Amano et al. 1996). Several roles of PRK1 in cytoskeletal regulation have been described, including phosphorylation of vimentin (Matsuzawa et al. 1997), neurofilament assembly disruption (Manser et al. 2008), interaction with the actin crosslinking protein α-actinin (Mukai et al. 1997) and insulininduced stress fibre disruption (Dong et al. 2000). PRK1 has also been linked to androgen receptor signalling and Electronic supplementary material The online version of this article (doi:https://doi.org/10.1007/s12104-020-09954-7) contains supplementary material, which is available to authorized users. * Helen R. Mott [email protected] 1
Department of Biochemistry, 80, Tennis Court Road, Cambridge CB2 1GA, UK
Present Address: Department of Pathology, 10, Tennis Court Road, Cambridge CB2 1QP, UK
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transcriptional regulation (Metzger et al. 2003, 2008), the immune response (Park et al. 2016), cell cycle progression (Schmidt et al. 2007), thromboxane signalling (O’Sullivan et al. 2015) and mTOR signalling (Yang et al. 2017; Wallroth et al. 2019). PRK1 is overexpressed in human prostate cancer (Metzger et al. 2003; O’Sullivan et al. 2017) and has also been implicated in ovarian cancer (Galgano et al. 2009) and in the migration of bladder tumour cells (Lachmann et al. 2011). PRK1 has three N-terminal HR1 domains, HR1a, HR1b and HR1c. These are antiparallel coiled coils of approximately 10 kDa that interact with the nucleotide-sensitive switch regi
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