Protein kinase CK2 catalyzes tyrosine phosphorylation in mammalian cells.
Protein kinase CK2 exhibits oncogenic activity in mice and is over-expressed in a number of tumors or leukemic cells. On the basis of its amino acid sequence and a wealth of experimental information, CK2 has traditionally been classified as a protein serine/threonine kinase. In contrast to this traditional view of CK2, recent evidence has shown that CK2 can also phosphorylate tyrosine residues under some circumstances in vitro and in yeast. In this study, we provide definitive evidence demonstrating that CK2 also exhibits tyrosine kinase activity in mammalian cells. Tyrosine phosphorylation of CK2 in cells and in CK2 immunoprecipitates is dependent on CK2 activity and is inhibited by the CK2 selective inhibitor 4,5,6,7-tetrabromobenzotriazole. Examination of phosphotyrosine profiles in cells reveals a number of proteins, including CK2 itself, which exhibit increased tyrosine phosphorylation when CK2 levels are increased. Peptide arrays to evaluate the specificity determinants for tyrosine phosphorylation by CK2 reveal that its specificity for tyrosine phosphorylation is distinct from its specificity for serine/threonine phosphorylation. Of particular note is the requirement for an aspartic acid immediately C-terminal to the phosphorylatable tyrosine residue. Collectively, these data provide conclusive evidence that CK2 catalyzes the phosphorylation of tyrosine residues in mammalian cells, a finding that adds a new level of complexity to the challenge of elucidating its cellular functions. Furthermore, these results raise the possibility that increased CK2 levels that frequently accompany transformation may contribute to the increased tyrosine phosphorylation that occurs in transformed cells.
Vilk
Greg
G
Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
Weber
Jane E
JE
Turowec
Jacob P
JP
Duncan
James S
JS
Wu
Chenggang
C
Derksen
D Richard
DR
Zien
Piotr
P
Sarno
Stefania
S
Donella-Deana
Arianna
A
Lajoie
Gilles
G
Pinna
Lorenzo A
LA
Li
Shawn S C
SS
Litchfield
David W
DW
D000595:Amino Acid Sequence; D047390:Casein Kinase II / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis / Q000187:drug effects; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D020035:Holoenzymes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism*; D040081:Protein Array Analysis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D055503:Protein Multimerization; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects
D020035:Holoenzymes; D050505:Mutant Proteins; D047428:Protein Kinase Inhibitors; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D047390:Casein Kinase II