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 LKB1 regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. We find that SNRK is not active when expressed in HeLa cells that lack expression of LKB1, and its activity is restored by expression of wild type LKB1, but not catalytically deficient LKB1. 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 LKB1. 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 LKB1.
Jaleel
Mahaboobi
M
MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK. a.mahaboobi@dundee.ac.uk
McBride
Andrew
A
Lizcano
Jose M
JM
Deak
Maria
M
Toth
Rachel
R
Morrice
Nick A
NA
Alessi
Dario R
DR
D055372:AMP-Activated Protein Kinases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D004789:Enzyme Activation; D005285:Fermentation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity; D013395:Sucrose / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D013395:Sucrose; C490994:SNRK protein, human; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases