The 25-kDa FK506-binding protein is localized in the nucleus and associates with casein kinase II and nucleolin.
FK506-binding proteins (FKBPs) have been identified as the cellular receptors of the immunosuppressive drugs FK506 and rapamycin. Recently, we cloned a 25-kDa FKBP family member (FKBP25) and found that FKBP25 contains a nuclear localization sequence and several potential casein kinase II phosphorylation sites. It has been previously shown that phosphorylation of proteins by casein kinase II can enhance their nuclear localization. Here we demonstrate that FKBP25 is localized to the nucleus and that a glutathione S-transferase fusion protein of FKBP25 (GST-FKBP25) can be phosphorylated by casein kinase II. Also a stable FKBP25/casein kinase II complex was formed when the GST-FKBP25 fusion protein was incubated either with purified casein kinase II or with cell lysates. Furthermore, when GST-FKBP25 was incubated with nuclear lysates, nucleolin, a major nuclear substrate of casein kinase II, was found associated with the GST-FKBP25/casein kinase II complex. Casein kinase II phosphorylation of several cytosolic and nuclear substrates, including nucleolin, appears to be important for the regulation of cell growth. The interaction of FKBP25 with casein kinase II may regulate these functions.
Jin
Y J
YJ
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Burakoff
S J
SJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D047390:Casein Kinase II; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D016601:RNA-Binding Proteins; D013601:T-Lymphocytes; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins; D000097796:Nucleolin
D000596:Amino Acids; D002352:Carrier Proteins; D047390:Casein Kinase II; D009687:Nuclear Proteins; D009842:Oligopeptides; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D016601:RNA-Binding Proteins; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins; D000097796:Nucleolin