PMID- 16413928
OWN - NLM
STAT- MEDLINE
DCOM- 20060323
LR  - 20210108
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 71
IP  - 5
DP  - 2006 Feb 28
TI  - 14-3-3zeta interacts with human thromboxane receptors and is involved in the 
      agonist-induced activation of the extracellular-signal-regulated kinase.
PG  - 624-33
AB  - Thromboxane receptor (TP) signaling results in a broad range of cellular 
      responses including kinase activation and subsequent nuclear signaling events 
      involved in cell transformation, proliferation, and cell survival. Proteins that 
      may participate in the early signaling following receptor activation remain to be 
      identified. We found that 14-3-3zeta is a novel protein interacting with TP 
      intracellular loop 3 (i3) by yeast two-hybrid system. This interaction was 
      further confirmed by GST pull-down and co-immunoprecipitation methods. 
      Site-directed mutagenesis studies indicated that Pro-236 of the TP-i3 was 
      involved in the binding to the 14-3-3zeta. Co-immunoprecipitation studies in the 
      same cell lysate by TP antibody showed that TP binds not only with the 14-3-3zeta 
      but also with the Raf-1. Our data also demonstrated that TP receptor activation 
      induced by agonist rapidly recruited 14-3-3zeta and Raf-1 to form a complex with 
      the TP on the plasma membrane. The significance of assembling this protein 
      complex was examined by TP agonist-induced extracellular-signal-regulated kinase 
      (ERK) phosphorylation in intact cells. TP agonist, I-BOP, induced ERK 
      phosphorylation in HEK 293 cells expressing wild type TPalpha but significantly 
      lower in those expressing TPalpha-P236V mutant. Attenuation of the expression of 
      14-3-3zeta by 14-3-3zeta siRNA decreased I-BOP-induced ERK phosphorylation 
      indicating the involvement of the 14-3-3zeta in the signal transduction process. 
      These results suggest that 14-3-3zeta may serve as a scaffold protein to form a 
      protein complex consisting of TP, 14-3-3zeta, and Raf-1, and that this protein 
      complex may be involved in the activation of ERK pathway following TP receptor 
      activation.
FAU - Yan, Weili
AU  - Yan W
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Kentucky, Lexington, KY 40536-0082, USA.
FAU - Ding, Yunfei
AU  - Ding Y
FAU - Tai, Hsin-Hsiung
AU  - Tai HH
LA  - eng
GR  - HL 46296/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060104
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Receptors, Thromboxane)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - 14-3-3 Proteins/*metabolism
MH  - Blotting, Western
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Humans
MH  - Immunoprecipitation
MH  - Protein Binding
MH  - Receptors, Thromboxane/*metabolism
EDAT- 2006/01/18 09:00
MHDA- 2006/03/24 09:00
CRDT- 2006/01/18 09:00
PHST- 2005/10/04 00:00 [received]
PHST- 2005/11/22 00:00 [revised]
PHST- 2005/11/28 00:00 [accepted]
PHST- 2006/01/18 09:00 [pubmed]
PHST- 2006/03/24 09:00 [medline]
PHST- 2006/01/18 09:00 [entrez]
AID - S0006-2952(05)00792-6 [pii]
AID - 10.1016/j.bcp.2005.11.027 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2006 Feb 28;71(5):624-33. doi: 10.1016/j.bcp.2005.11.027. Epub 
      2006 Jan 4.