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Fyn phosphorylates AMPK to inhibit AMPK activity and AMP-dependent activation of autophagy.


ABSTRACT: We previously demonstrated that proto-oncogene Fyn decreased energy expenditure and increased metabolic phenotypes. Also Fyn decreased autophagy-mediated muscle mass by directly inhibiting LKB1 and stimulating STAT3 activities, respectively. AMPK, a downstream target of LKB1, was recently identified as a key molecule controlling autophagy. Here we identified that Fyn phosphorylates the ? subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex. As pro-inflammatory mediators are reported modulators of the autophagy processes, treatment with the pro-inflammatory cytokine TNF? resulted in 1) increased Fyn activity 2) stimulated Fyn-dependent AMPK? tyrosine phosphorylation and 3) decreased AICAR-dependent AMPK activation. Importantly, TNF? induced inhibition of autophagy was not observed when AMPK? was mutated on Y436. 4) These data demonstrate that Fyn plays an important role in relaying the effects of TNF? on autophagy and apoptosis via phosphorylation and inhibition of AMPK.

SUBMITTER: Yamada E 

PROVIDER: S-EPMC5340180 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Fyn phosphorylates AMPK to inhibit AMPK activity and AMP-dependent activation of autophagy.

Yamada Eijiro E   Okada Shuichi S   Bastie Claire C CC   Vatish Manu M   Nakajima Yasuyo Y   Shibusawa Ryo R   Ozawa Atsushi A   Pessin Jeffrey E JE   Yamada Masanobu M  

Oncotarget 20161101 46


We previously demonstrated that proto-oncogene Fyn decreased energy expenditure and increased metabolic phenotypes. Also Fyn decreased autophagy-mediated muscle mass by directly inhibiting LKB1 and stimulating STAT3 activities, respectively. AMPK, a downstream target of LKB1, was recently identified as a key molecule controlling autophagy. Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK  ...[more]

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