Identification of the sucrose non‐fermenting related kinase SNRK, as a novel LKB1 substrate
Open Access
- 1 February 2005
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 579 (6), 1417-1423
- https://doi.org/10.1016/j.febslet.2005.01.042
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- Expression analysis of the human testis-specific serine/threonine kinase (TSSK) homologues. A TSSK member is present in the equatorial segment of human spermMolecular Human Reproduction, 2004
- Crystal structure of MO25α in complex with the C terminus of the pseudo kinase STE20-related adaptorNature Structural & Molecular Biology, 2004
- MO25 / interact with STRAD / enhancing their ability to bind, activate and localize LKB1 in the cytoplasmThe EMBO Journal, 2003
- Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRADThe EMBO Journal, 2003
- A role for Drosophila LKB1 in anterior–posterior axis formation and epithelial polarityNature, 2003
- Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2Cytogenetic and Genome Research, 2002
- Peutz-Jeghers syndrome is caused by mutations in a novel serine threoninekinaseNature Genetics, 1998
- Similar substrate recognition motifs for mammalian AMP‐activated protein kinase, higher plant HMG‐CoA reductase kinase‐A, yeast SNF1, and mammalian calmodulin‐dependent protein kinase IFEBS Letters, 1995
- Characterization of a novel murine testis-specific serine/threonine kinaseGene, 1994