Phosphorylation of c-Abl by γ-PAK in vitro.
(A) A cartoon of the c-Abl domains SH3, SH2, kinase, and
the C-terminal domain. The latter contains proline-rich sequences A, B,
C, D, and E; three nuclear localization signals (NLS); one nuclear
export signal (NES); and DNA-binding and actin-binding domains. The
Crk/CrkL family of CF adaptor proteins binds to proline-rich
sequences A and B, whereas the Nck and Abi adaptors bind to
proline-rich sequence C. (B, Upper) c-Abl
expressed in insect cells was immunoprecipitated and phosphorylated
with γ-PAK activated by caspase 3 as described in Experimental
Procedures and analyzed by SDS/PAGE. (B,
Lower) GST-fusion proteins of c-Abl fragments were
phosphorylated with activated γ-PAK and subjected to SDS/PAGE.
Lanes 1 and 6, no substrate; lanes 2 and 7, c-Abl 593–730; lanes 3 and
8, c-Abl SH2; lanes 4 and 9, c-Abl SH3; lanes 5 and 10, c-Abl SH2–SH3
K290R. (C, Upper) Tryptic phosphopeptide
mapping was carried out on Abl 593–730 and Abl SH2–SH1 K290R
phosphorylated by γ-PAK. Arrows indicate the origin.
(C, Lower) Phosphoamino acid analysis of
Abl 593–730 and Abl SH2–SH1 K290R phosphorylated by γ-PAK. In all
instances, radiolabeled phosphate was detected by using a
PhosphorImager system. O, origin; TP, phosphothreonine; YP,
phosphotyrosine; SP, phosphoserine.