The JI Acurri Cytometers
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xie, Z.-H.
Right arrow Articles by Siraganian, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xie, Z.-H.
Right arrow Articles by Siraganian, R. P.
The Journal of Immunology, 2002, 168: 4682-4691.
Copyright © 2002 by The American Association of Immunologists

The Adapter Molecule Gab2 Regulates Fc{epsilon}RI-Mediated Signal Transduction in Mast Cells

Zhi-Hui Xie*, Indu Ambudkar{dagger} and Reuben P. Siraganian1,*

* Receptors and Signal Transduction Section, Oral Infection and Immunity Branch, and {dagger} Secretory Physiology Section, Gene Therapy and Therapeutics Branch, Department of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892

The recently cloned scaffolding molecule Gab2 can assemble multiple molecules involved in signaling pathways. Bone marrow-derived mast cells isolated from Gab2-/- mice have defective signaling probably due to the lack of the activation of phosphatidylinositol-3 kinase (PI3-kinase). In this study, we investigated the role of Gab2 using the rat basophilic leukemia 2H3 cell line mast cells. Fc{epsilon}RI aggregation induced the tyrosine phosphorylation of Gab2 and translocation of a significant fraction of it from the cytosol to the plasma membrane. As in other cells, Gab2 was found to associate with several signaling molecules including Src homology 2-containing protein tyrosine phosphatase 2, Grb2, Lyn, and phospholipase C{gamma} (PLC{gamma}). The association of Gab2 with Lyn and PLC{gamma} were enhanced after receptor aggregation. Overexpression of Gab2 in rat basophilic leukemia 2H3 cell line cells inhibited the Fc{epsilon}RI-induced tyrosine phosphorylation of the subunits of the receptor, and the phosphorylation and/or activation of Syk and mitogen-activated protein kinase. Downstream events such as calcium mobilization, degranulation, and induction of TNF-{alpha} and IL-6 gene transcripts were decreased in Gab2 overexpressing cells, although Akt phosphorylation as a measure of PI3-kinase activation was unaffected. These results suggest that in addition to the positive effects mediated by PI3-kinase that are apparent in Gab2-/- mast cells, Gab2 by interacting with Lyn and PLC{gamma} may have negative regulatory effects on Fc{epsilon}RI-induced mast cell signaling and functions.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
S. M. Shahjahan Miah, T. L. Hughes, and K. S. Campbell
KIR2DL4 Differentially Signals Downstream Functions in Human NK Cells through Distinct Structural Modules
J. Immunol., March 1, 2008; 180(5): 2922 - 2932.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Draberova, G. M. Shaik, P. Volna, P. Heneberg, M. Tumova, P. Lebduska, J. Korb, and P. Draber
Regulation of Ca2+ Signaling in Mast Cells by Tyrosine-Phosphorylated and Unphosphorylated Non-T Cell Activation Linker
J. Immunol., October 15, 2007; 179(8): 5169 - 5180.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Chen, B. P. Pappu, H. Zeng, L. Xue, S. W. Morris, X. Lin, R. Wen, and D. Wang
B Cell Lymphoma 10 Is Essential for Fc{epsilon}R-Mediated Degranulation and IL-6 Production in Mast Cells
J. Immunol., January 1, 2007; 178(1): 49 - 57.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. M. Udell, L. A. Samayawardhena, Y. Kawakami, T. Kawakami, and A. W. B. Craig
Fer and Fps/Fes Participate in a Lyn-dependent Pathway from Fc{epsilon}RI to Platelet-Endothelial Cell Adhesion Molecule 1 to Limit Mast Cell Activation
J. Biol. Chem., July 28, 2006; 281(30): 20949 - 20957.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. V. Parry, G. C. Whittaker, M. Sims, C. E. Edmead, M. J. Welham, and S. G. Ward
Ligation of CD28 Stimulates the Formation of a Multimeric Signaling Complex Involving Grb-2-Associated Binder 2 (Gab2), Src Homology Phosphatase-2, and Phosphatidylinositol 3-Kinase: Evidence That Negative Regulation of CD28 Signaling Requires the Gab2 Pleckstrin Homology Domain
J. Immunol., January 1, 2006; 176(1): 594 - 602.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. M. Vonakis, S. P. Gibbons Jr, M. J. Rotte, E. A. Brothers, S. C. Kim, K. Chichester, and S. M. MacDonald
Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (Fc{epsilon}RI)
J. Immunol., October 1, 2005; 175(7): 4543 - 4554.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
K. Nishida, S. Yamasaki, Y. Ito, K. Kabu, K. Hattori, T. Tezuka, H. Nishizumi, D. Kitamura, R. Goitsuka, R. S. Geha, et al.
Fc{varepsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane
J. Cell Biol., July 4, 2005; 170(1): 115 - 126.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
S. Kraft, T. Fleming, J. M. Billingsley, S.-Y. Lin, M.-H. Jouvin, P. Storz, and J.-P. Kinet
Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo
J. Exp. Med., February 7, 2005; 201(3): 385 - 396.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Hitomi, J. Zhang, L. M. Nicoletti, A. C. G. Grodzki, M. C. Jamur, C. Oliver, and R. P. Siraganian
Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation
Blood, December 15, 2004; 104(13): 4122 - 4128.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
P. Volna, P. Lebduska, L. Draberova, S. Simova, P. Heneberg, M. Boubelik, V. Bugajev, B. Malissen, B. S. Wilson, V. Horejsi, et al.
Negative Regulation of Mast Cell Signaling and Function by the Adaptor LAB/NTAL
J. Exp. Med., October 18, 2004; 200(8): 1001 - 1013.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
O. Malbec, M. Malissen, I. Isnardi, R. Lesourne, A.-M. Mura, W. H. Fridman, B. Malissen, and M. Daeron
Linker for Activation of T Cells Integrates Positive and Negative Signaling in Mast Cells
J. Immunol., October 15, 2004; 173(8): 5086 - 5094.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Q.-S. Zhu, L. J. Robinson, V. Roginskaya, and S. J. Corey
G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses
Blood, May 1, 2004; 103(9): 3305 - 3312.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
X. Qu, K. Sada, S. Kyo, K. Maeno, S. M. S. Miah, and H. Yamamura
Negative regulation of Fc{epsilon}RI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b
Blood, March 1, 2004; 103(5): 1779 - 1786.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Zhang, E. Berenstein, and R. P. Siraganian
Phosphorylation of Tyr342 in the Linker Region of Syk Is Critical for Fc{varepsilon}RI Signaling in Mast Cells
Mol. Cell. Biol., December 1, 2002; 22(23): 8144 - 8154.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.