Cystic fibrosis transmembrane regulator fragments with the Phe508 deletion exert a dual allosteric control over the master kinase CK2.

Cystic fibrosis mostly follows a single Phe508 deletion in CFTR (cystic fibrosis transmembrane regulator) (CFTR?F508), thereby causing premature fragmentation of the nascent protein with concomitant alterations of diverse cellular functions. We show that CK2, the most pleiotropic protein kinase, undergoes allosteric control of its different cellular forms in the presence of short CFTR peptides encompassing the Phe508 deletion: these CFTR?F508 peptides drastically inhibit the isolated catalytic subunit (?) of the kinase and yet up-regulate the holoenzyme, composed of two catalytic and two non-catalytic (? ) subunits. Remarkable agreement between in silico docking and our biochemical data point to different sites for the CFTR?F508 peptide binding on isolated CK2? and on CK2? assembled into the holoenzyme, suggesting that CK2 targeting may be perturbed in cells expressing CFTR?F508; this could shed light on some pleiotropic aspects of cystic fibrosis disease.