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Investigating the Role of 3‐Phosphoinositide‐Dependent Protein Kinase 1 in the Spatiotemporal Regulation of the Purinosome
Author(s) -
Sundaram Anand,
An Songon
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.573.26
Subject(s) - kinase , microbiology and biotechnology , protein kinase b , pi3k/akt/mtor pathway , phosphoinositide 3 kinase , phosphorylation , biology , chemistry , signal transduction , small molecule , biochemistry
The enzymes involved in human de novo purine biosynthesis form a transient multienzyme complex, the “purinosome,” under purine starvation. To determine cellular regulatory mechanisms of purinosome assembly/disassembly, fluorescence live‐cell imaging has been used to monitor purinosome dynamics following small molecular inhibition/activation of protein kinases involved in cell signaling. To date, we observe that pharmacological inhibition of 3‐phosphoinositide‐dependent protein kinase 1 (PDK1) resulted in purinosome formation, but not purinosome dissociation, in HeLa and Hs578T cells. Subsequent inhibition of protein kinase C, one of downstream kinases of PDK1, resulted in purinosome formation as well. However,small‐molecule inhibition of other downstream targets of PDK1, including Akt and mammalian Target of Rapamycin (mTOR), exhibited no effect on purinosome assembly. We hypothesize that PDK1‐associated signaling pathways negatively regulate purinosome formation in an Akt‐independent manner. Collectively, our work has the potential to demonstrate the functional role of PDK1 on de novo purine biosynthesis, thus providing a novel target for anti‐cancer drug discovery.