Abstract
Phosphorylation of the signaling component by protein kinase often leads to a kinase cascade or feedback loop. 3-Phosphoinositide- dependent kinase 1 (PDK1) signaling pathway diverges into various kinases including Akt and p70 S6 kinase (p70S6k). However, the PDK1 feedback mechanism remains elusive. Here, we demonstrated that UNC-51-like kinase (ULK1), an autophagy initiator kinase downstream of mechanistic target of rapamycin (mTOR), directly phosphorylated PDK1 on serine 389 at the linker region. Furthermore, our data showed that this phosphorylation affected the kinase activity of PDK1 toward downstream substrates. These results suggest a possible negative feedback loop between PDK1 and ULK1. [BMB Reports 2020; 53(7): 373-378].
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases / metabolism*
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Autophagy
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Autophagy-Related Protein-1 Homolog / metabolism*
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HEK293 Cells
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism*
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Phosphatidylinositol 3-Kinase / metabolism
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Phosphatidylinositols
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Phosphorylation
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Proto-Oncogene Proteins c-akt / metabolism
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism
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Serine / metabolism
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Signal Transduction
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TOR Serine-Threonine Kinases
Substances
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Intracellular Signaling Peptides and Proteins
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Phosphatidylinositols
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Serine
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MTOR protein, human
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Phosphatidylinositol 3-Kinase
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3-Phosphoinositide-Dependent Protein Kinases
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Autophagy-Related Protein-1 Homolog
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PDPK1 protein, human
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases, 70-kDa
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TOR Serine-Threonine Kinases
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ULK1 protein, human