PubMed Journals: J Biol Chem
Source: PMID: 10542228
⇦ ⇨ J Biol Chem. 1999 Nov 5;274(45):31981-6.
The role of DOC-2/DAB2 protein phosphorylation
in the inhibition of AP-1 activity. An underlying
mechanism of its tumor-suppressive function
in prostate cancer.
Tseng CP(1), Ely BD, Pong RC, Wang Z, Zhou
J, Hsieh JT.
(1) Department of Urology,
University of Texas Southwestern Medical Center,
Dallas, Texas 75235-9110, USA.
DOC-2/DAB2, a novel phosphoprotein with signal-transducing
capability, inhibits human prostatic cancer
cells (Tseng, C.-P., Ely, B. D., Li, Y.,
Pong, R.-C., and Hsieh, J.-T. (1998) Endocrinology
139, 3542-3553). However, its mechanism
of action is not understood completely.
This study delineates the functional significance
of DOC-2/DAB2 protein phosphorylation and
demonstrates that in vivo activation of
protein kinase C (PKC) by
induces DOC-2/DAB2 phosphorylation, including
a serine residue at position 24. Mutation
of Ser(24) to Ala reduced DOC-2/DAB2 phosphorylation
by PKC. Using a synthetic Ser(24) peptide
(APS(24)KKEKKKGSEKTD) or recombinant DOC-2/DAB2
as substrates, PKCbetaII, PKCgamma, and
PKCdelta (but not casein kinase II) directly
phosphorylated Ser(24) in vitro. This indicates
that DOC-2/DAB2 is a PKC-specific substrate.
Since expression of wild-type DOC-2/DAB2,
but not the S24A mutant, inhibited TPA-induced
AP-1 activity in prostatic epithelial cells,
phosphorylation of Ser(24) appears to play
a critical role in modulating TPA-induced
AP-1 activity. Taken together, these data
suggest that PKC-regulated phosphorylation
of DOC-2/DAB2 protein may help its growth
PMID: 10542228 [Indexed for MEDLINE]