3 research outputs found
c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK)
The VRK1 kinase is a novel Ser-Thr kinase in the human
kinome that diverged from the casein kinase 1 branch.
These kinases phosphorylate transcription factors related
to stress responses, such as p53. In this report we have
studied the phosphorylation of the transcription factor
c-Jun in its N-terminal region. The VRK1 protein
phosphorylates c-Jun with a Km of 0.4 lM, and is not
inhibited by SP600125. VRK1 phosphorylates c-Jun in
Ser63 and Ser73 in vitro, the same residues targeted by
the N-terminal kinase of c-Jun (JNK). This phosphorylation
induces the stabilization and accumulation of the c-
Jun protein. VRK1 phosphorylates the endogenous c-Jun
in Ser63. VRK1 activates c-Jun dependent transcription,
which is dependent on phosphorylation of Ser63 and
Ser73. The c-Jun with Ser63Ala and Ser73Ala substitutions
is not transcriptionally active when cotransfected
with VRK1. VRK1 interacts with c-Jun but not with JNK.
The cotransfection of VRK1 and JNK has an additive
effect on the transcriptional activation of c-Jun indicating
that they can cooperate when both are at suboptimal dose;
otherwise, maximum effect by one of them prevents the
effect of the other. The VRK1-c-Jun connection represents
a component of a new signaling pathway whose
upstream elements remain to be identified.Peer reviewe