Title : PKD1 Inhibits AMPKα2 through Phosphorylation of Serine 491 and Impairs Insulin Signaling in Skeletal Muscle Cells.

Pub. Date : 2016 Mar 11

PMID : 26797128






7 Functional Relationships(s)
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1 Exposure to a high glucose concentration has recently been shown to increase phosphorylation of AMPK at Ser(485/491) of its alpha1/alpha2 subunit; however, the mechanism by which it does so is not known. Serine protein kinase AMP-activated catalytic subunit alpha 2 Homo sapiens
2 We sought to determine whether PKC or PKD1 is involved in inhibition of AMPK by causing Ser(485/491) phosphorylation in skeletal muscle cells. Serine protein kinase AMP-activated catalytic subunit alpha 2 Homo sapiens
3 This caused dose- and time-dependent increases in AMPK Ser(485/491) phosphorylation, which was associated with a ~60% decrease in AMPKalpha2 activity. Serine protein kinase AMP-activated catalytic subunit alpha 2 Homo sapiens
4 This caused dose- and time-dependent increases in AMPK Ser(485/491) phosphorylation, which was associated with a ~60% decrease in AMPKalpha2 activity. Serine protein kinase AMP-activated catalytic subunit alpha 2 Homo sapiens
5 Genetic knockdown of PKD1 also prevented Ser(485/491) phosphorylation of AMPK. Serine protein kinase AMP-activated catalytic subunit alpha 2 Homo sapiens
6 Finally, recombinant PKD1 phosphorylated AMPKalpha2 at Ser(491) in cell-free conditions. Serine protein kinase AMP-activated catalytic subunit alpha 2 Homo sapiens
7 These results identify PKD1 as a novel upstream kinase of AMPKalpha2 Ser(491) that plays a negative role in insulin signaling in muscle cells. Serine protein kinase AMP-activated catalytic subunit alpha 2 Homo sapiens