|
|
Blood, 1 December 2003, Vol. 102, No. 12, pp. 3998-4005.
Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2003-04-1149.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Regulation of tissue factor cytoplasmic domain phosphorylation by palmitoylation
Andrea Dorfleutner, and
Wolfram Ruf
From the Department of Immunology, The Scripps Research Institute, La Jolla, CA.
The tissue factor (TF)–initiated coagulation pathway plays important roles in hemostasis, inflammation, metastasis, and angiogenesis. Phosphorylation of the TF cytoplasmic domain is functionally relevant in metastasis. How TF cytoplasmic domain phosphorylation downstream of protein kinase C (PKC) activation is regulated in primary vascular cells remains poorly understood. Here, phosphorylation of Ser258, rather than the PKC consensus site Ser253, is identified as the major conformational switch required for recognition by a phosphorylation-specific antibody. With this novel reagent, we demonstrate that the TF cytoplasmic domain is primarily unphosphorylated in confluent endothelial cells. TF cytoplasmic domain phosphorylation can occur in the absence of the autologous TF transmembrane and extracellular domains but requires maturation of TF in the Golgi compartment and cell surface expression. Site-directed mutagenesis and 2-bromopalmitate treatment provide evidence that palmitoylation of the cytoplasmic Cys245 is a negative regulatory mechanism of Ser258 phosphorylation. Profiling with PKC-selective inhibitors identifies PKC as important for TF cytoplasmic domain phosphorylation. Mutagenesis of protein kinase consensus sites are consistent with a model in which PKC-dependent phosphorylation of Ser253 enhances subsequent Ser258 phosphorylation by a Pro-directed kinase. Thus, cell surface location–dependent phosphorylation of the TF cytoplasmic domain is regulated at multiple levels.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Russo, U. J. K. Soh, and J. Trejo
Proteases Display Biased Agonism at Protease-Activated Receptors: Location matters!
Mol. Interv.,
April 1, 2009;
9(2):
87 - 96.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bhattacharjee, J. Ahamed, R. Pawlinski, C. Liu, N. Mackman, W. Ruf, and T. S. Edgington
Factor Xa Binding to Annexin 2 Mediates Signal Transduction via Protease-Activated Receptor 1
Circ. Res.,
February 29, 2008;
102(4):
457 - 464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Versteeg, F. Schaffner, M. Kerver, H. H. Petersen, J. Ahamed, B. Felding-Habermann, Y. Takada, B. M. Mueller, and W. Ruf
Inhibition of tissue factor signaling suppresses tumor growth
Blood,
January 1, 2008;
111(1):
190 - 199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. V. Kovalenko, X. H. Yang, and M. E. Hemler
A Novel Cysteine Cross-linking Method Reveals a Direct Association between Claudin-1 and Tetraspanin CD9
Mol. Cell. Proteomics,
November 1, 2007;
6(11):
1855 - 1867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Versteeg and W. Ruf
Tissue Factor Coagulant Function Is Enhanced by Protein-disulfide Isomerase Independent of Oxidoreductase Activity
J. Biol. Chem.,
August 31, 2007;
282(35):
25416 - 25424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. K. Mandal, U. R. Pendurthi, and L. V. M. Rao
Tissue factor trafficking in fibroblasts: involvement of protease-activated receptor-mediated cell signaling
Blood,
July 1, 2007;
110(1):
161 - 170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Ott, C. Michaelis, M. Schuermann, B. Steppich, I. Seitz, M. Dewerchin, D. Zohlnhofer, R. Wessely, M. Rudelius, A. Schomig, et al.
Vascular Remodeling in Mice Lacking the Cytoplasmic Domain of Tissue Factor
Circ. Res.,
August 5, 2005;
97(3):
293 - 298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Belting, J. Ahamed, and W. Ruf
Signaling of the Tissue Factor Coagulation Pathway in Angiogenesis and Cancer
Arterioscler Thromb Vasc Biol,
August 1, 2005;
25(8):
1545 - 1550.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bhattacharjee, J. Ahamed, B. Pedersen, A. El-Sheikh, N. Mackman, W. Ruf, C. Liu, and T. S. Edgington
Regulation of Tissue Factor-Mediated Initiation of the Coagulation Cascade by Cell Surface Grp78
Arterioscler Thromb Vasc Biol,
August 1, 2005;
25(8):
1737 - 1743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-P. Fortin, G. E. Rivard, A. Adam, and F. Marceau
Studies on rabbit natural and recombinant tissue factors: intracellular retention and regulation of surface expression in cultured cells
Am J Physiol Heart Circ Physiol,
May 1, 2005;
288(5):
H2192 - H2202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ahamed, M. Belting, and W. Ruf
Regulation of tissue factor-induced signaling by endogenous and recombinant tissue factor pathway inhibitor 1
Blood,
March 15, 2005;
105(6):
2384 - 2391.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. V. M. Rao and U. R. Pendurthi
Tissue Factor-Factor VIIa Signaling
Arterioscler Thromb Vasc Biol,
January 1, 2005;
25(1):
47 - 56.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dorfleutner, E. Hintermann, T. Tarui, Y. Takada, and W. Ruf
Cross-talk of Integrin {alpha}3{beta}1 and Tissue Factor in Cell Migration
Mol. Biol. Cell,
October 1, 2004;
15(10):
4416 - 4425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ahamed and W. Ruf
Protease-activated Receptor 2-dependent Phosphorylation of the Tissue Factor Cytoplasmic Domain
J. Biol. Chem.,
May 28, 2004;
279(22):
23038 - 23044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
