M. Desclozeaux et al., PHOSPHORYLATION OF AN N-TERMINAL MOTIF ENHANCES DNA-BINDNG ACTIVITY OF THE HUMAN SRY PROTEIN, The Journal of biological chemistry, 273(14), 1998, pp. 7988-7995
Of the several strategies that eukaryotes have evolved to modulate tra
nscription factor activity, phosphorylation is regarded as one of the
major mechanisms in signal-dependent transcriptional control, To concl
usively demonstrate that the human sex-determining gene SRY is affecte
d by such a post-translational control mechanism, we have analyzed its
phosphorylation status in living cells. in the present study, we show
that the cyclic AMP-dependent protein kinase (PKA) phosphorylates the
human SRY protein in vitro as well as in vivo on serine residues loca
ted in the N-terminal part of the protein, This phosphorylation event
was shown to positively regulate SRY DNA-binding activity and to enhan
ce the ability of SRY to inhibit a basal promoter activity located dow
nstream of an SRY DNA-binding site concatamer. Together these results
strongly support the hypothesis that human SRY is a natural substrate
for PKA in vivo and that this phosphorylation significantly modulates
its major activity, DNA-binding, thereby possibly altering its biologi
cal function.