PMID- 10542228
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - 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.
PG  - 31981-6
AB  - 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 12-O-tetradecanoylphorbol-13-acetate
      (TPA) 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 inhibitory function.
FAU - Tseng, C P
AU  - Tseng CP
AD  - Department of Urology, University of Texas Southwestern Medical Center, Dallas,
      Texas 75235-9110, USA.
FAU - Ely, B D
AU  - Ely BD
FAU - Pong, R C
AU  - Pong RC
FAU - Wang, Z
AU  - Wang Z
FAU - Zhou, J
AU  - Zhou J
FAU - Hsieh, J T
AU  - Hsieh JT
LA  - eng
GR  - CA59939/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (DAB2 protein, human)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis Regulatory Proteins
MH  - COS Cells
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Prostatic Neoplasms/*metabolism
MH  - Protein Kinase C/metabolism
MH  - Proteins/*metabolism
MH  - Serine/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factor AP-1/*antagonists & inhibitors
MH  - Tumor Suppressor Proteins
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.31981 [doi]
AID - S0021-9258(19)51516-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):31981-6. doi: 10.1074/jbc.274.45.31981.