Akt phosphorylation at Thr308 and Ser473 - (Jul/31/2015 )

Dear All,

I am studying Akt signaling pathway. I know that phosphorylation at both T308 and S473 is prerequisite for full activation of Akt but wonder if phosphorylation/de-phosphorylation of one of them is prerequisite for another.

In other words,

1. wonder if phosphorylation at T308 is required for phosphorylation at S473 or vice versa, or they are phosphorylated independently.

2. wonder if de-phosphorylation at T308 is required for de-phosphorylation at S473 or vice versa, or they are de-phosphorylated independently (wonder if there is any order of de-phosphorylation by phosphatases such as PP2A between the two sites)

If there is such order, can anyone suggests me some references?

Thank you so much in advance.

C 

This is not as easy as you may think, Akt physiology, and in fact virtually every protein's physiology is not as simple as weather it is phosphorylated or not.  For example, the O-GlcNAc modification, a special type of glycosylation of intracellular proteins that is akin to the Yin to the Yang of phosphorylation significantly regulates Akt's phosphorylation and function.  O-glcnac regulates the phospho patterns of Akt directly at the S473, so you you have to worry about much more than just phosphatases that act on S473:

http://www.ncbi.nlm.nih.gov/pubmed/18570920

Additionally, modification of Akt by O-glcnac at completely different sites on Akt can even regulate how it is phosphorylated at S473:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030422/

Agree. These references may help:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2141899/

http://www.mtoz-biolabs.com/phospho-proteomics.html

https://www.cell.com/cell/pdf/S0092-8674(17)30413-0.pdf