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p70S6K is regulated by focal adhesion kinase and is required for Src-selective autophagy.

Sandilands E, Schoenherr C, Frame MC - Cell. Signal. (2015)

Bottom Line: Specifically, in SCCs that are genetically deficient for FAK, there is reduced phosphorylation of Akt, p70S6K and S6, and signalling to Akt-p70S6K-S6 is more sensitive to inhibition by multiple agents that suppress the pathway.This is associated with loss of a complex between p-Src and the autophagy protein LC3, a biochemical surrogate of impaired Src-selective autophagy.We therefore deduce that the FAK-regulated signalling module PDK1-Akt-p70S6K that controls Src's intracellular trafficking operates at Src-containing autophagosomes.

View Article: PubMed Central - PubMed

Affiliation: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, United Kingdom.

No MeSH data available.


Related in: MedlinePlus

The PDK1/Akt/p70S6K pathway is linked to Src-selective autophagy. FAK-WT and FAK −/− cells were treated with the inhibitors A–F for 24 h. (A) Cell lysates were immunoblotted with anti-FAK, anti-p-PDK1 S241, anti-PDK1, anti-p-Akt S473, anti-Akt and anti-GAPDH. Graphs show the relative ratio of phospho-Akt S473/total Akt. (B) Cell lysates were immunoblotted with anti-p-p70S6K T389, anti-p70S6K, anti-p-S6 S235/236, anti-p-S6 S240/244, anti-S6 and anti-GAPDH. Graphs show the relative ratio of p-S6 S235/236/total S6.
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f0015: The PDK1/Akt/p70S6K pathway is linked to Src-selective autophagy. FAK-WT and FAK −/− cells were treated with the inhibitors A–F for 24 h. (A) Cell lysates were immunoblotted with anti-FAK, anti-p-PDK1 S241, anti-PDK1, anti-p-Akt S473, anti-Akt and anti-GAPDH. Graphs show the relative ratio of phospho-Akt S473/total Akt. (B) Cell lysates were immunoblotted with anti-p-p70S6K T389, anti-p70S6K, anti-p-S6 S235/236, anti-p-S6 S240/244, anti-S6 and anti-GAPDH. Graphs show the relative ratio of p-S6 S235/236/total S6.

Mentions: We investigated the effects of the 6 pharmacological agents (A–F). All inhibitors (with the exception of one, namely inhibitor C) caused a robust reduction in p-PDK1 and total PDK1, particularly notable in FAK-deficient cells. Treatment with inhibitor C resulted in a small increase in total PDK1 in FAK −/− cells (Fig. 3A). All 6 inhibitors caused reduced phosphorylation of Akt, most prominently in FAK-deficient cells (Fig. 3A, quantified in lower panels).


p70S6K is regulated by focal adhesion kinase and is required for Src-selective autophagy.

Sandilands E, Schoenherr C, Frame MC - Cell. Signal. (2015)

The PDK1/Akt/p70S6K pathway is linked to Src-selective autophagy. FAK-WT and FAK −/− cells were treated with the inhibitors A–F for 24 h. (A) Cell lysates were immunoblotted with anti-FAK, anti-p-PDK1 S241, anti-PDK1, anti-p-Akt S473, anti-Akt and anti-GAPDH. Graphs show the relative ratio of phospho-Akt S473/total Akt. (B) Cell lysates were immunoblotted with anti-p-p70S6K T389, anti-p70S6K, anti-p-S6 S235/236, anti-p-S6 S240/244, anti-S6 and anti-GAPDH. Graphs show the relative ratio of p-S6 S235/236/total S6.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508348&req=5

f0015: The PDK1/Akt/p70S6K pathway is linked to Src-selective autophagy. FAK-WT and FAK −/− cells were treated with the inhibitors A–F for 24 h. (A) Cell lysates were immunoblotted with anti-FAK, anti-p-PDK1 S241, anti-PDK1, anti-p-Akt S473, anti-Akt and anti-GAPDH. Graphs show the relative ratio of phospho-Akt S473/total Akt. (B) Cell lysates were immunoblotted with anti-p-p70S6K T389, anti-p70S6K, anti-p-S6 S235/236, anti-p-S6 S240/244, anti-S6 and anti-GAPDH. Graphs show the relative ratio of p-S6 S235/236/total S6.
Mentions: We investigated the effects of the 6 pharmacological agents (A–F). All inhibitors (with the exception of one, namely inhibitor C) caused a robust reduction in p-PDK1 and total PDK1, particularly notable in FAK-deficient cells. Treatment with inhibitor C resulted in a small increase in total PDK1 in FAK −/− cells (Fig. 3A). All 6 inhibitors caused reduced phosphorylation of Akt, most prominently in FAK-deficient cells (Fig. 3A, quantified in lower panels).

Bottom Line: Specifically, in SCCs that are genetically deficient for FAK, there is reduced phosphorylation of Akt, p70S6K and S6, and signalling to Akt-p70S6K-S6 is more sensitive to inhibition by multiple agents that suppress the pathway.This is associated with loss of a complex between p-Src and the autophagy protein LC3, a biochemical surrogate of impaired Src-selective autophagy.We therefore deduce that the FAK-regulated signalling module PDK1-Akt-p70S6K that controls Src's intracellular trafficking operates at Src-containing autophagosomes.

View Article: PubMed Central - PubMed

Affiliation: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, United Kingdom.

No MeSH data available.


Related in: MedlinePlus