Autocatalytic tyrosine-phosphorylation of protein kinase CK2 alpha and alpha' 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) tyrosine-autophosphorylation, which is dependent on intrinsic catalytic activity and is suppressed by the individual mutation of Tyr182, a crucial residue of the activation loop, to phenylalanine. At variance with serine-autophosphorylation, tyrosine-autophosphorylation of CK2alpha is reversed by ADP and GDP and is counteracted by the beta-subunit and by a peptide reproducing the activation loop of CK2alpha/alpha' (amino acids 175-201). These results disclose new perspectives about the mode of regulation of CK2 catalytic subunits.
Donella-Deana
A
A
Dipartimento di Chimica Biologica and Centro di Studio delle Biomembrane del C.N.R., University of Padova, Padova, Italy.
Cesaro
L
L
Sarno
S
S
Brunati
A M
AM
Ruzzene
M
M
Pinna
L A
LA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D047390:Casein Kinase II; D004642:Emodin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010649:Phenylalanine; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014443:Tyrosine
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D021122:Protein Subunits; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D010649:Phenylalanine; D000255:Adenosine Triphosphate; D006493:Heparin; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D004642:Emodin