Reply to Shears: As knowledge of inositol pyrophosphates advances, wonder recedes

Wonder is the seed of knowledge. Francis Bacon We are pleased by the interest our manuscript has generated. Shears’s interpretation of our data (1) demonstrates the constructive discussion necessary to enable forward progress in the exciting and still nascent concept of protein pyrophosphorylation by inositol pyrophosphates. In his letter (2), Shears interprets the in vitro back-pyrophosphorylation of AP3B1 by [32P]IP7 data as a potential indication of inositol pyrophosphates’ regulation of casein-kinase II (CK2). In his view, CK2 activity could be augmented in the absence of IP7, better priming AP3B1 for subsequent in vitro pyrophosphorylation by IP7 (3). In this scenario, …