The Caenorhabditis elegans AMP-activated Protein Kinase AAK-2 Is Phosphorylated by LKB1 and Is Required for Resistance to Oxidative Stress and for Normal Motility and Foraging Behavior

Jeong Soo Cho,Se-Jin Lee,Hyeon-Sook Koo,Tae Hoon Lee,Nils Lambacher,Anton Gartner,Hyojin Lee,Jieun Lee

doi:10.1074/jbc.m709115200

Jeong Soo Cho, Se-Jin Lee + Show 6 more

Open Access

https://doi.org/10.1074/jbc.m709115200

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Abstract

AAK-2 is one of two alpha isoforms of the AMP-activated protein kinase in Caenorhabditis elegans and is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. We found that AAK-2 was phosphorylated at threonine 243 in response to paraquat treatment and that this phosphorylation depends on PAR-4, the C. elegans LKB1 homologue. Both aak-2 mutation and par-4 knockdown increased the sensitivity of C. elegans worms to paraquat, and the double deficiency did not further increase sensitivity, indicating that aak-2 and par-4 act in a linear pathway. Both mutations also slowed body bending during locomotion and failed to reduce head oscillation in response to anterior touch. Consistent with this abnormal motility and behavioral response, expression of the AAK-2::green fluorescent protein fusion protein was observed in the ventral cord, some neurons, body wall muscle, pharynx, vulva, somatic gonad, and excretory cell. Our study suggests that AMPK can influence the behavior of C. elegans worms in addition to its well known function in metabolic control.

Highlights

AMP-activated protein kinase (AMPK)3 is activated by low glucose intake, extensive physical exercise, and various stresses such as oxidative stress, hypoxia, ischemia, and heat shock [1]
Given that aak-2 worms show a reduced life span [9], a pheno- blotted extracts from transgenic worms containing GFP-tagged type often correlated with oxidative stress, we directly tested AAK-2 and confirmed a band that was dramatically enhanced the effect of oxidative stress on the survival of wild-type and in extracts from paraquat-treated worms at the predicted aak-2 mutant worms
In Drosophila, an LKB1 homologue was demonstrated to be an upstream kinase of AMPK, which is essential for normal development and survival [7, 15]

Summary

Introduction

AMP-activated protein kinase (AMPK)3 is activated by low glucose intake, extensive physical exercise, and various stresses such as oxidative stress, hypoxia, ischemia, and heat shock [1]. We demonstrate that the C. elegans homologue of LKB1, PAR-4, is the upstream kinase of the AAK-2 AMPK ␣ subunit and that PAR-4 and AAK-2 deficiency sensitizes worms to oxidative stress.

Results

Conclusion