Macroautophagy (hereafter referred to as autophagy) is an evolutionarily 
conserved catabolic process necessary for normal recycling of cellular 
constituents and for appropriate response to cellular stress. Although several 
genes belonging to the core molecular machinery involved in autophagosome 
formation have been discovered, relatively little is known about the nature of 
signaling networks controlling autophagy upon intracellular or extracellular 
stimuli. We discovered ATG8-like proteins (MAP1LC3B, GABARAP and GABARAPL1) as 
novel interactors of MAPK15/ERK8, a MAP kinase involved in cell proliferation 
and transformation. Based on the role of these proteins in the autophagic 
process, we demonstrated that MAPK15 is indeed localized to autophagic 
compartments and increased, in a kinase-dependent fashion, ATG8-like proteins 
lipidation, autophagosome formation and SQSTM1 degradation, while decreasing 
LC3B inhibitory phosphorylation. Interestingly, we also identified a conserved 
LC3-interacting region (LIR) in MAPK15 responsible for its interaction with 
ATG8-like proteins, for its localization to autophagic structures and, 
consequently, for stimulation of the formation of these compartments. 
Furthermore, we reveal that MAPK15 activity was induced in response to serum and 
amino-acid starvation and that this stimulus, in turn, required endogenous 
MAPK15 expression to induce the autophagic process. Altogether, these results 
suggested a new function for MAPK15 as a regulator of autophagy, acting through 
interaction with ATG8 family proteins. Also, based on the key role of this 
process in several human diseases, these results supported the use of this MAP 
kinase as a potential novel therapeutic target.