Polo-like kinase 1-mediated phosphorylation of the GTP-binding protein Ran is important for bipolar spindle formation.
Polo-like kinase functions are essential for the establishment of a normal bipolar mitotic spindle, although precisely how Plk1 regulates the spindle is uncertain. In this study, we report that the small GTP/GDP-binding protein Ran is associated with Plk1. Plk1 is capable of phosphorylating co-immunoprecipitated Ran in vitro on serine-135 and Ran is phosphorylated in vivo at the same site during mitosis when Plk1 is normally activated. Cell cultures over-expressing a Ran S135D mutant have significantly higher numbers of abnormal mitotic cells than those over-expressing either wild-type or S135A Ran. The abnormalities in S135D mutant cells are similar to cells over-expressing Plk1. Our data suggests that Ran is a physiological substrate of Plk1 and that Plk1 regulates the spindle organization partially through its phosphorylation on Ran.
Feng
Yang
Y
Laboratory of Cancer Prevention, NCI at Frederick, Frederick, MD, USA; Nanobiology Program, CCR, NCI at Frederick, Frederick, MD, USA. yfeng@mail.ncifcrf.gov
Yuan
Jin Hui
JH
Maloid
Sharon C
SC
Fisher
Rebecca
R
Copeland
Terry D
TD
Longo
Dan L
DL
Conrads
Thomas P
TP
Veenstra
Timothy D
TD
Ferris
Andrea
A
Hughes
Steve
S
Dimitrov
Dimiter S
DS
Ferris
Douglass K
DK
D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004285:Dogs; D006160:Guanosine Triphosphate / Q000737:chemistry; D006801:Humans; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D012694:Serine / Q000737:chemistry; D020931:ran GTP-Binding Protein / Q000737:chemistry; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012694:Serine; D020931:ran GTP-Binding Protein; D000097869:Polo-Like Kinase 1