Phosphorylation of CKBBP2/CRIF1 by protein kinase CKII promotes cell proliferation.
CKII plays a significant role in cell proliferation and cell cycle control. In this report, yeast two-hybrid assay and pull-down assay demonstrate that CKBBP2/CRIF1 associates with the beta subunit of CKII in vitro and in vivo. Recombinant CKBBP2/CRIF1 is phosphorylated in vitro by purified CKII and by CKII inhibitor apigenin-sensitive protein kinase in HEK293 cell extract. Phosphoamino acid analysis and mutational analysis indicate that CKII phosphorylates serine at residue 221 within CKBBP2/CRIF1. Furthermore, serine to alanine mutation at residue 221 abrogates the phosphorylation of CKBBP2/CRIF1 observed in HEK293 cell extract, indicating that CKII is a major kinase that is responsible for phosphorylation of CKBBP2/CRIF1. As compared with the wild-type CKBBP2/CRIF1 or nonphosphorylatable mutant CKBBP2(S221A) (in which the serine-221 is replaced by alanine), overexpression of CKBBP2(S221E) in COS7 cells promotes cell proliferation. Taken together, the present results suggest that CKII may be involved in cell proliferation, at least in part, through the phosphorylation of serine-221 within CKBBP2/CRIF1.
Oh
Nang-Soo
NS
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Yoon
Soo-Hyun
SH
Lee
Won-Kyu
WK
Choi
Je-Yong
JY
Min
Do Sik
do S
Bae
Young-Seuk
YS
D000818:Animals; D019556:COS Cells; D047390:Casein Kinase II / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation
D018797:Cell Cycle Proteins; C476586:GADD45GIP1 protein, human; D009687:Nuclear Proteins; D047390:Casein Kinase II