Novel roles of PRK1 and PRK2 in cilia and cancer biology.

Scientific Reports
Hitesh PatelMargaret Frame

Abstract

PRK1 and PRK2 are two closely related AGC-family serine/threonine protein kinases. Here we demonstrate novel roles for them at cilia and in cancer biology. In both instances serum withdrawal leads to increased activating PRK1 and PRK2 phosphorylation (pPRK1/pPRK2) and their depletion results in reduced spheroid growth. pPRK1/pPRK2 localise to the transition zone of cilia and their co-depletion results in reduced cilia size, impaired planer polarity and impaired cilia associated signalling. High PRK2 (but not PRK1) expression correlates with poor outcome in patients with basal-like/Triple Negative (TN) Breast Cancer (BC) where there is also higher expression relative to other BC tumour subtypes. In agreement, depletion of PRK1 and PRK2 in mouse TNBC cells, or CRISPR/Cas9 mediated deletion of PRK2 alone, significantly reduces cell proliferation and spheroid growth. Finally proteomic analysis to identify PRK2 binding partners in mouse TNBC cells revealed proteins that are important for both cilia and BC biology. Taken together these data demonstrate novel roles for PRK1 and PRK2 at cilia and in BC biology and in the case of PRK2 in particular, identifies it as a novel TNBC therapeutic target.

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Citations

Feb 2, 2021·Biochemical Society Transactions·Georgios SophocleousHelen R Mott
Aug 28, 2021·Cells·Dinu AntonyMiriam Schmidts
Sep 10, 2021·The Journal of Clinical Investigation·Young-June JinStefan Offermanns

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Methods Mentioned

BETA
GTPases
GTPase
transfection
FACS
immunoprecipitation

Software Mentioned

Depmap
Prism
ImageXpress
MetaXpress
ImageJ
MaxQuant
Fiji

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