Specific interaction between S6K1 and CoA synthase: a potential link between the mTOR/S6K pathway, CoA biosynthesis and energy metabolism.
Ribosomal protein S6 kinase (S6K) is a key regulator of cell size and growth. It is regulated via phosphoinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR) signaling pathways. We demonstrate for the first time that CoA synthase associates specifically with S6K1. The association was observed between native and transiently overexpressed proteins in vivo, as well as by BIAcore analysis in vitro. The sites of interaction were mapped to the C-terminal regions of both CoA synthase and S6K1. In vitro studies indicated that the interaction does not affect their enzymatic activities and that CoA synthase is not a substrate for S6 kinase. This study uncovers a potential link between mTor/S6K signaling pathway and energy metabolism through CoA and its thioester derivatives, but its physiological relevance should be further elucidated.
Nemazanyy
Ivan
I
Department of Structure and Function of Nucleic Acid, The Institute of Molecular Biology and Genetics, 150 Zabolotnogo St, Kyiv 03143, Ukraine.
Panasyuk
Ganna
G
Zhyvoloup
Alexander
A
Panayotou
George
G
Gout
Ivan T
IT
Filonenko
Valeriy
V
D000106:Acetate-CoA Ligase / Q000096:biosynthesis* / Q000737:chemistry; D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D048429:Cell Size; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D058570:TOR Serine-Threonine Kinases
D000106:Acetate-CoA Ligase; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human