RETRACTED: Protein kinase CK2 acts as a signal molecule switching between the NDPK-A/AMPK α1 complex and NDPK-B (Retracted Article. See vol 21, pg 3398, 2007)

Previously we elucidated the molecular interaction between the nucleoside diphosphate kinase A ( NDPK-A)/AMP-activated protein kinase ( AMPK) alpha 1 complex, discovering a process we termed "substrate channeling." Here, we investigate the protein-protein interaction of the substrate channeling complex with the pleiotropic protein kinase, CK2 ( formerly casein kinase 2). We show that CK2 is part of the NDPK-A/AMPK alpha 1 complex under basal ( background AMPK activity) conditions, binding directly to each of the complex components independently. We report that when S122 on NDPK-A is phosphorylated by AMPK alpha 1 in vivo, ( i.e., stimulation of AMPK using either metformin or phenformin) initiating the substrate channeling mechanism, the catalytic subunit of CK2 ( CK2 alpha) is expelled from the complex and translocates to bind NDPK-B, a closely related but independent isoform of NDPK. Thus, we find that the AMPK-dependent phosphostatus of S122 on NDPK-A determines whether CK2 alpha swaps partners between NDPK-A and NDPK-B. This is the first reported linkage between NDPK-A and NDPK-B via a phosphorylation pathway and could explain the complex biology of NDPK. This study also offers an explanation as to how CK2 alpha exclusion mutations ( S120A or S122D of NDPK-A) on NDPK-A might have implications in cancer biology and general cellular energy metabolism.