Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition.

and ENSA are inhibitors of protein phosphatase PP2A. and ENSA phosphorylated by Greatwall kinase inhibit PP2A during mitosis. is expressed in striatal neurons where basal phosphorylation by MAST3 kinase inhibits PP2A and regulates key components of striatal signaling. The proteins were discovered as substrates for but the function of phosphorylation is unknown. We find that phosphorylation by duanyu1529 or MAST3 mutually suppresses the ability of the other kinase to act on Phosphorylation by duanyu1529 also acts to prevent inhibition of PP2A by duanyu37P-16 phosphorylated by MAST3. Moreover, duanyu1529 phosphorylates MAST3 at multiple sites resulting in its inhibition. Mathematical modeling highlights the role of these three regulatory interactions to create a switch-like response to cAMP. Together, the results suggest a complex antagonistic interplay between the control of duanyu37P-16 by MAST3 and duanyu1529 that creates a mechanism whereby cAMP mediates PP2A disinhibition.

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