Phylogenomics of phosphoinositide lipid kinases: perspectives on the evolution of second messenger signaling and drug discovery |
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Authors: | James R Brown and Kurt R Auger |
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Institution: | (1) Computational Biology, Quantitative Sciences, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, P.O. Box 5089, 19426-0989 Collegeville, PA, USA;(2) Cancer Epigenetics, Oncology R&D, GlaxoSmithKline, 1250 South Collegeville Road, UP1110, P.O. Box 5089, 19426-0989 Collegeville, PA, USA |
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Abstract: | Background Phosphoinositide lipid kinases (PIKs) generate specific phosphorylated variants of phosatidylinositols (PtdIns) that are critical
for second messenger signaling and cellular membrane remodeling. Mammals have 19 PIK isoforms spread across three major families:
the PtIns 3-kinases (PI3Ks), PtdIns 4-kinases (PI4Ks), and PtdIns-P (PIP) kinases (PIPKs). Other eukaryotes have fewer yet
varying PIK complements. PIKs are also an important, emerging class of drug targets for many therapeutic areas including cancer,
inflammatory and metabolic diseases and host-pathogen interactions. Here, we report the genomic occurrences and evolutionary
relationships or phylogenomics of all three PIK families across major eukaryotic groups and suggest potential ramifications
for drug discovery. |
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