|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 September 2000, Vol. 96, No. 6, pp. 2199-2205
IMMUNOBIOLOGY
Phosphatidylinositol-3 kinase regulates p21ras
activation during IgE-mediated stimulation of
human basophils
Katsushi Miura and
Donald
W. MacGlashan Jr
From the Johns Hopkins Asthma and Allergy Center,
Baltimore, MD.
Cross-linking of IgE or a bacterial product (f-Met-Leu-Phe;
FMLP) induces the release of leukotriene C4 (LTC4) and histamine in
human basophils. However, the signaling mechanisms in human basophils
are only partially understood. It has been demonstrated that
extracellular signal-regulated kinases (ERK1/2) specifically regulate
the pathway for LTC4 generation, but not for histamine release and
interleukin-4 production. More recent studies have suggested that
tyrosine kinase (syk)-mediated phosphorylation of shc is responsible
for the ras-ERK cascade via the formation of shc-Grb2-Sos2 following
stimulation with anti-IgE antibody, but not FMLP, in human basophils.
However, while characterizing the role of phosphatidylinositol (PI)-3
kinase in signaling pathways leading to basophil mediator release, it
was noted that this pathway might also regulate p21ras activation.
Anti-IgE antibody, but not FMLP, resulted in phosphorylation of p85
(regulatory subunit of PI3 kinase), suggesting activation of PI3
kinase. Inhibition of PI3 kinase by selective inhibitor (LY294002)
abolished anti-IgE antibody- but not FMLP-induced phosphorylation of
MEK1 (MAPK kinase/ERK kinase) and ERKs while inhibiting LTC4 generation
as well as histamine release. IgE-mediated activation of ras (upstream
of MEK-ERK) was also inhibited. But, further upstream, phosphorylation
of syk and of shc and inducible association between shc and Grb2 were
not affected. Furthermore, the IgE-mediated cytosolic calcium response
([Ca++]i) was also diminished. These results
suggest that functional responses may be dependent on the activity of
PI3 kinase, which regulates at least 2 important signaling pathways: by
regulating activation of ras for the MEK-ERK pathway and the increase
in [Ca++]i.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Kneidinger, U. Schmidt, U. Rix, K. V. Gleixner, A. Vales, C. Baumgartner, C. Lupinek, M. Weghofer, K. L. Bennett, H. Herrmann, et al.
The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils
Blood,
March 15, 2008;
111(6):
3097 - 3107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. MacGlashan Jr.
Endocytosis, recycling, and degradation of unoccupied Fc{epsilon}RI in human basophils
J. Leukoc. Biol.,
October 1, 2007;
82(4):
1003 - 1010.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Vilarino, K. Miura, and D. W. MacGlashan Jr
Acute IL-3 Priming Up-Regulates the Stimulus-Induced Raf-1-Mek-Erk Cascade Independently of IL-3-Induced Activation of Erk
J. Immunol.,
September 1, 2005;
175(5):
3006 - 3014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. F. Gibbs, K. E. S. Plath, H. H. Wolff, and J. Grabbe
Regulation of mediator secretion in human basophils by p38 mitogen-activated protein kinase: phosphorylation is sensitive to the effects of phosphatidylinositol 3-kinase inhibitors and calcium mobilization
J. Leukoc. Biol.,
August 1, 2002;
72(2):
391 - 400.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Jacob, D. Cooney, M. Pradhan, and K. M. Coggeshall
Convergence of Signaling Pathways on the Activation of ERK in B Cells
J. Biol. Chem.,
June 21, 2002;
277(26):
23420 - 23426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Miura, S. Lavens-Phillips, and D. W. MacGlashan Jr.
Localizing a Control Region in the Pathway to Leukotriene C4 Secretion Following Stimulation of Human Basophils with Anti-IgE Antibody
J. Immunol.,
December 15, 2001;
167(12):
7027 - 7037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. MacGlashan Jr and S. Lavens-Phillips
Characteristics of the free cytosolic calcium timelag following IgE-mediated stimulation of human basophils: significance for the nonreleasing basophil phenotype
J. Leukoc. Biol.,
February 1, 2001;
69(2):
224 - 232.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T.-T. Ching, A.-L. Hsu, A. J. Johnson, and C.-S. Chen
Phosphoinositide 3-Kinase Facilitates Antigen-stimulated Ca2+ Influx in RBL-2H3 Mast Cells via a Phosphatidylinositol 3,4,5-Trisphosphate-sensitive Ca2+ Entry Mechanism
J. Biol. Chem.,
April 27, 2001;
276(18):
14814 - 14820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bandeira-Melo, M. Phoofolo, and P. F. Weller
Extranuclear Lipid Bodies, Elicited by CCR3-mediated Signaling Pathways, Are the Sites of Chemokine-enhanced Leukotriene C4 Production in Eosinophils and Basophils
J. Biol. Chem.,
June 15, 2001;
276(25):
22779 - 22787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Takeda, T. Ichiki, T. Tokunou, N. Iino, and A. Takeshita
15-Deoxy-Delta 12,14-prostaglandin J2 and Thiazolidinediones Activate the MEK/ERK Pathway through Phosphatidylinositol 3-Kinase in Vascular Smooth Muscle Cells
J. Biol. Chem.,
December 21, 2001;
276(52):
48950 - 48955.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
