|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 2037-2043
A critical role for PI 3-kinase in cytokine-induced Fc -receptor
activation
Madelon Bracke,
Evert Nijhuis,
Jan-Willem J. Lammers,
Paul J. Coffer, and
Leo Koenderman
From the Department of Pulmonary Diseases, University Medical
Center, Utrecht, The Netherlands.
Fc-receptors, such as Fc R and Fc RII, play an important role in
leukocyte activation, and rapid modulation of ligand binding ("activation") is critical for receptor regulation. We have
previously demonstrated that ligand binding to Fc-receptors on human
eosinophils is dependent on cytokine stimulation. Utilization of
pharmacological inhibitors provided evidence that the phenomenon of
interleukin (IL)-5 induced immunoglobulin A (IgA) binding to human
eosinophils requires activation of phosphatidylinositol 3-kinase
(PI3K). However, eosinophils are refractory to manipulation by
molecular techniques such as DNA transfection or viral infection. Here
we utilize an IL-3 dependent pre-B cell line to investigate the
molecular mechanism of cytokine-mediated ligand binding to FcR. In
this system, IgA binding is dependent on IL-3, similarly to the
requirement for IL-5 of eosinophils. We show that IL-3-mediated
activation of FcR (CD89) requires the activation of PI3K,
independent of p21ras activation. Co-expression of dominant negative
( p85) and active (p110_K227E) forms of PI3K demonstrate that the
affinity switch regulating FcR activation requires PI3K. Moreover,
overexpression of PI3K is both necessary and sufficient for activation
of FcR. Furthermore, we show that IL-3/IL-5/GM-CSF induced
inside-out signaling pathways activating FcR require the involvement
of protein kinase C downstream of PI3K. Finally, we show that these inside-out signaling pathways responsible for Fc-receptor modulation require CD89, independent of its association with the FcR chain.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. E. Bakema, A. Bakker, S. de Haij, H. Honing, M. Bracke, L. Koenderman, G. Vidarsson, J. G. J. van de Winkel, and J. H. W. Leusen
Inside-Out Regulation of Fc{alpha}RI (CD89) Depends on PP2A
J. Immunol.,
September 15, 2008;
181(6):
4080 - 4088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Boyle, N. F. Brown, J. H. Brumell, and B. B. Finlay
Src homology domain 2 adaptors affect adherence of Salmonella enterica serovar Typhimurium to non-phagocytic cells
Microbiology,
October 1, 2007;
153(10):
3517 - 3526.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Myou, A. R. Leff, S. Myo, E. Boetticher, A. Y. Meliton, A. T. Lambertino, J. Liu, C. Xu, N. M. Munoz, and X. Zhu
Activation of Group IV Cytosolic Phospholipase A2 in Human Eosinophils by Phosphoinositide 3-Kinase Through a Mitogen-Activated Protein Kinase-Independent Pathway
J. Immunol.,
October 15, 2003;
171(8):
4399 - 4405.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhu, B. Jacobs, E. Boetticher, S. Myou, A. Meliton, H. Sano, A. T. Lambertino, N. M. Munoz, and A. R. Leff
IL-5-induced integrin adhesion of human eosinophils caused by ERK1/2-mediated activation of cPLA2
J. Leukoc. Biol.,
November 1, 2002;
72(5):
1046 - 1053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pilette, Y. Ouadrhiri, V. Godding, J-P. Vaerman, and Y. Sibille
Lung mucosal immunity: immunoglobulin-A revisited
Eur. Respir. J.,
September 1, 2001;
18(3):
571 - 588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Wines, C. T. Sardjono, H. M. Trist, C.-S. Lay, and P. M. Hogarth
The Interaction of Fc{{alpha}}RI with IgA and Its Implications for Ligand Binding by Immunoreceptors of the Leukocyte Receptor Cluster
J. Immunol.,
February 1, 2001;
166(3):
1781 - 1789.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bracke, E. van de Graaf, J.-W. J Lammers, P. J Coffer, and L. Koenderman
In vivo priming of Fc{alpha}R functioning on eosinophils of allergic asthmatics
J. Leukoc. Biol.,
November 1, 2000;
68(5):
655 - 661.
[Abstract]
[Full Text]
|
|
|
|
|
