Section Bank B/B #44

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betterfuture

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Can anyone explain this. This doesn't make sense. How can PKA only partially activate CREB327?

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GSK-3 phosphorylates CREB at ser115 and PKA phosphorylates CREB at ser119. In Table 1, the control levels represent low to no CREB activity and the CREB327WT levels represent normal CREB activity (assuming both ser sites are phosphorylated).

CREB327-115 can't be phosphorylated at ser115 (by GSK-3) and shows an activity level of 8.5 (higher than the control).

CREB327-119 can't be phosphorylated at ser119 (by PKA) and shows an activity level of 1.7 (similar to the control).

Since CREB327-115 shows activity above control levels when it's phosphorylated by PKA, PKA looks like it can partially activate CREB, but not fully activate it up to the levels of CREB327WT.

This is just based on the data interpretation, though. We wouldn't know mechanistically how the partial activation is working.
 
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I think I am reading too much into the wording. When I read, PKA can only partially activate CREB327, I thought it meant that somehow PKA doesn't complete it's phosphorylation on the CREB327, like maybe one of the phosphate groups became nonfunctional somehow.

I didn't read it like, PKA phosphorylates CREB327 to activate it, but not to the extent that a normal activation would be by both PKA and GSK-3.
 
I think I am reading too much into the wording. When I read, PKA can only partially activate CREB327, I thought it meant that somehow PKA doesn't complete it's phosphorylation on the CREB327, like maybe one of the phosphate groups became nonfunctional somehow.

I didn't read it like, PKA phosphorylates CREB327 to activate it, but not to the extent that a normal activation would be by both PKA and GSK-3.

Oh yeah, your second interpretation is spot on. Figures 1 and 2 kind of hint at this. For CREB327-WT, the GSK lane alone is blank, but the PKA + GSK-3 lane shows more phosphorylation than just the PKA lane. This is implying that CREB327-WT phosphorylation seems to happen in sequence with GSK-3 only being able to phosphorylate CREB after PKA.

So the "partial phosphorylation" could be something where only PKA does phosphorylation instead of PKA + GSK-3.
 
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