Compounds are non toxic, but they decrease both AKT and pAKT expression level.
Hello Debasis,
It is a good question and you'll have several answers; however, with a decrease in the expression of AKT and p-AKT you could investigate whether the levels of PDK1 is higher. PDK1 is known to phosphorylate AKT.
The PI3K phosphorylates PIP2 into PIP3 that plays an important role in AKT phosphorylation. On the other hand, PTEN is a plasma-membrane lipid phosphatase that acts as an antagonist of the PI3K. With PTEN levels are reduced, the levels of p-AKT will likely increase.
You should also check mTOR levels, since mTOR is also able to phosphorylate AKT.
These players could well explain the reduction on p-AKT levels, but I'm not sure if would explain reduction on AKT levels.
I hope it helped.
Dear Leonardo,
Thank you for your response. I agree with you regarding the modification in pAKT level. However, decrease in total AKT level in additio to decrease in pAKT level is not clear to me.
Debasis
Dear Debasis,
It is indeed interesting and it's not usual in my opinion.
However, I found some very interesting papers regarding this issue that might help you.
In summary, mTOR plays an important role in AKT degradation through phosphorylation. Now, AKT degradation can be due to ubiquitination, caspase cleavage, and other factors.
http://www.ncbi.nlm.nih.gov/pubmed/21321111
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826820/
I hope it helps.
Leonardo
Dear Leonardo,
Thank you for your response. Yes, these are few possible ways. I will check those possibilities.
Debasis
Even I would like to know if you could figure out what was the possible reason? Very interesting question! Thank you
Did some of you figured out a possible mechanims? I observe the same in my western blot analyses using several PI3K inhibitors. Thank you!
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