PRKAR1A mutation and Pituitary adenoma

[Ebtesam]

Hi, Im a medical student and was studying pathology when I came across the genetic mutations associated with pituitary adenomas. Amongst the mutations was a gain-of-function mutation of the Protein Kinase A, regulatory subunit 1 (PRKAR1A) gene.

I am confused as to how a gain-of-function mutation of the PRKAR1A gene leads to unregulated cAMP activity as PRKAR1A encodes a negative regulator of Protein Kinase A. So, shouldn't a gain-of-function mutation lead to supressed activity of Protein Kinase A?

[Dagl1]

I think you may misunderstand the meaning of gain of function; it does not (have to) mean that the protein is more efficient, rather it just means that the protein gains novel functions. I am however unfamiliar with Pituitary Adenoma so I looked it up in relation to PRKAR1a and it mentions that loss of PRKAR1a leads to those types of cancers, not the other way around. 

Possibly the gain of function mutation alters the gene expression to result in less PRKAR1a overall? Can you send me the source where you found the Gain of Function part?

-Dagl