| First Author | Tominaga Y | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 19 | Pages | 8465-75 |
| PubMed ID | 16166629 | Mgi Jnum | J:101366 |
| Mgi Id | MGI:3603888 | Doi | 10.1128/MCB.25.19.8465-8475.2005 |
| Citation | Tominaga Y, et al. (2005) Translational deregulation in PDK-1-/- embryonic stem cells. Mol Cell Biol 25(19):8465-75 |
| abstractText | PDK-1 is a protein kinase that is critical for the activation of many downstream protein kinases in the AGC superfamily, through phosphorylation of the activation loop site on these substrates. Cells lacking PDK-1 show decreased activity of these protein kinases, including protein kinase B (PKB) and p70S6K, whereas mTOR activity remains largely unaffected. Here we show, by assessing both association of cellular RNAs with polysomes and by metabolic labeling, that PDK-1-/- embryonic stem (ES) cells exhibit defects in mRNA translation. We identify which mRNAs are most dramatically translationally regulated in cells lacking PDK-1 expression by performing microarray analysis of total and polysomal RNA in these cells. In addition to the decreased translation of many RNAs, a smaller number of RNAs show increased association with polyribosomes in PDK-1-/- ES cells relative to PDK-1+/+ ES cells. We show that PKB activity is a critical downstream component of PDK-1 in mediating translation of cystatin C, RANKL, and Rab11a, whereas mTOR activity is less important for effective translation of these targets. |
