PerspectiveBiochemistry

A perspective on AKT 25-plus years after its discovery

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Science Signaling  04 Jul 2017:
Vol. 10, Issue 486, eaan8791
DOI: 10.1126/scisignal.aan8791

Figures

  • Fig. 1 AKT targets are distinctly modulated by differential phosphorylation of active (Thr305-phosphorylated) AKT3.

    The phosphorylation of a set of AKT substrates and the abundance of a set of proteins encoded from potential AKT target genes are modulated differently when AKT3 is phosphorylated at sites in tandem with Thr305 (the “T-loop” phosphorylation site required for kinase activation). Therefore, such phosphorylation events may alter the signaling output and the cellular behavior elicited by Thr305-phosphorylated AKT. The present heatmap is proof of principle for a strategy that may offer clues to the biological significance of posttranslational modifications of AKT that are frequently observed in various cancers. Further analyses are needed to thoroughly address statistical strength and confidence. The heatmap was generated from data on 105 cases of breast cancer available in the CPTAC Data Portal (https://cptac-data-portal.georgetown.edu/cptacPublic/) (11) that we accessed through the cBioPortal pipeline (https://github.com/cBioPortal/CPTAC-proteomics-pipeline) (12), which combined the proteomics and phosphoproteomics data in a single file and eliminated three tumors that had been assayed as technical replicates. [Identical results can be obtained by downloading the data from the cBioPortal repository (www.cbioportal.org/study?id=brca_tcga) in a format directly importable to downstream analyses.] The phosphorylation and expression events in the heatmap were selected because they were the most robust across the set of 102 tumors we analyzed. Each cell in the heatmap presents the mean relative abundance of a protein or a phosphorylated protein in tumors that exhibited dual phosphorylation of AKT3 at Thr305 and another site. Relative values in individual cells were centered and standardized using row z scores; warmer colors correspond to higher relative abundance.

    CREDIT: A. KITTERMAN/SCIENCE SIGNALING

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