Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate

Recent work has shown that the LKB1 tumour suppressor protein kinase phosphorylates and activates protein kinases belonging to the AMP activated kinase (AMPK) subfamily. In this study, we identify the sucrose non-fermenting protein (SNF1)-related kinase (SNRK), a largely unstudied AMPK subfamily member, as a novel substrate for LKB1. We demonstrate that LKB1 activates SNRK by phosphorylating the T-loop residue (Thr173), and that the LKBI regulatory subunits STRAD and MO25 are required for LKBI to activate SNRK. We find that SNRK is not active when expressed in HeLa cells that lack expression of LKBI, and its activity is restored by expression of wild type LKBI, but not catalytically deficient LKBI. We also present evidence that two other AMPK-related kinases more distantly related to AMPK than SNRK, namely NIM1 and testis-specific serine/threonine kinase-1 (TSSK1) are not substrates for LKBI. Tissue distribution analysis indicates that SNRK protein is mainly expressed in testis, similar to TSSK isoforms, whereas NIM1 is more widely expressed. These results provide evidence that SNRK could mediate some of the physiological effects of LKBI. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.