Autocatalytic tyrosine-phosphorylation of protein kinase CK2 α and α′ subunits:: implication of Tyr182

CK2 is a pleiotropic and constitutively active serine/threonine protein kinase composed of two catalytic (alpha and/or alpha ') and two regulatory beta -subunits, whose mechanism of modulation is still obscure. Here we show that CK2 alpha/alpha ' subunits undergo intermolecular (trans) tyro sine-autophosphorylation, which is dependent on intrinsic catalytic activity and is suppressed by the individual mutation of Tyr(182), a crucial residue of the activation loop, to phenylalanine. At variance with serine-autophosphorylation, tyrosine-autophosphorylation of CK2 alpha is reversed by ADP and GDP and is counteracted by the beta -subunit and by a peptide reproducing the activation loop of CK2 alpha/alpha ' (amino acids 175-201). These results disclose new perspectives about the mode of regulation of CK2 catalytic subunits.