Phosphorylation of Ser-549 on Xwee1 by
Xchk1 mediates the binding of 14-3-3 proteins. (A) His6-Xchk1
phosphorylates full-length Xwee1 on Ser-549. Bacterially expressed
GST-Xwee1-WT (lanes 1 and 3) and GST-Xwee1-S549A (lanes 2 and 4) were
incubated with wild-type His6-Xchk1 (lanes 1 and 2) or kinase-inactive
His6-Xchk1-N135A (lanes 3 and 4). The kinase reactions were subjected
to SDS-PAGE and analyzed by autoradiography (top) and Coomassie blue
staining (bottom). (B) His6-Xchk1 phosphorylates a C-terminal peptide
derived from Xwee1. Bacterially expressed GST-Cdc25(254-316)-WT (lane
1), GST-Xwee1(475-555)-WT (lanes 2 and 4), and GST-Xwee1(475-555)-S549A
(lanes 3 and 5) were incubated with His6-Xchk1 (lanes 1–3) or
His6-Xchk1-N135A (lanes 4 and 5). The kinase reactions were processed
as in A. (C) Interphase egg extracts were subjected to
immunoprecipitation with control antibodies (lane 1) or anti-Xchk1
antibodies (lane 2). The resulting immunoprecipitates were assayed for
kinase activity toward GST-Xwee1(475-555)-WT (top) or
GST-Cdc25(254-316)-WT (bottom). The kinase reactions were then
processed for SDS-PAGE and autoradiography. (D) Ser-549 is a
physiological site of phosphorylation in interphase
Xenopus egg extracts. His6-GST-Xwee1 (left) and
His6-GST-Xwee1-S549A (right) were labeled with 32P and
subjected to two-dimensional tryptic phosphopeptide mapping as
described in MATERIALS AND METHODS. The position of the radioactive
spot that is missing from the map of the S549A mutant is marked with an
arrow. The mobility of this phosphopeptide was confirmed by
mixing the tryptic digests of the wild-type and S549A proteins.
The origin is indicated by a dot in the lower left-hand corner. (E)
GST-Xwee1(475-555)-WT (lanes 1–3) and GST-Xwee1(475-555)-S549A (lane
4), both of which were immobilized on glutathione agarose, were treated
with no kinase (lane 1), wild-type His6-Xchk1 (lanes 2 and 4), or
His6-Xchk1-N135A (lane 3) in the presence of ATP. Next, His6–14-3-3ε
was added to all four incubations. After extensive washing, bound
proteins were eluted with 50 mM glutathione, and the eluates were
analyzed by immunoblotting with anti-Xwee1 (top) or
anti-14-3-3ε (bottom) antibodies.