| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RI Signaling and Mast Cell Function1
* Abramson Family Cancer Research Institute and Department of Laboratory Medicine and Pathology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
Medical Scientist Training Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and
Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN 55455
The adapter molecule Src homology 2 (SH2) domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is essential for Fc
RI-mediated signaling, degranulation and IL-6 production in mast cells. To test the structural requirements of SLP-76 in mast cell signaling and function, we have studied the functional responses of murine bone marrow-derived mast cells (BMMCs) expressing mutant forms of SLP-76. We found that the N-terminal tyrosines as well as the central proline-rich region of SLP-76 are required for participation of SLP-76 in FcRI-mediated signaling and function. The C-terminal SH2 domain of SLP-76 also contributes to optimal function of SLP-76 in mast cells. Another adapter molecule, adhesion- and degranulation-promoting adapter protein (ADAP), is known to bind the SH2 domain of SLP-76, and cell line studies have implicated ADAP in mast cell adhesion and FcRI-induced degranulation. Surprisingly, we found that mast cells lacking ADAP expression demonstrate no defects in FcRI-induced adhesion, granule release, or IL-6 production, and that ADAP-deficient mice produce a normal passive systemic anaphylactic response. Thus, failure to bind ADAP does not underlie the functional defects exhibited by SLP-76 SH2 domain mutant-expressing mast cells.
This article has been cited by other articles:
|
|
 |
|
  S. Yamasaki, M. Takase-Utsugi, E. Ishikawa, M. Sakuma, K. Nishida, T. Saito, and O. Kanagawa Selective impairment of Fc{varepsilon}RI-mediated allergic reaction in Gads-deficient mice Int. Immunol., October 1, 2008; 20(10): 1289 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pazdrak, T. W. Young, S. Stafford, B. Olszewska-Pazdrak, C. Straub, V. Starosta, A. Brasier, and A. Kurosky Cross-Talk between ICAM-1 and GM-CSF Receptor Signaling Modulates Eosinophil Survival and Activation J. Immunol., March 15, 2008; 180(6): 4182 - 4190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Abtahian, N. Bezman, R. Clemens, E. Sebzda, L. Cheng, S. J. Shattil, M. L. Kahn, and G. A. Koretzky Evidence for the Requirement of ITAM Domains but Not SLP-76/Gads Interaction for Integrin Signaling in Hematopoietic Cells. Mol. Cell. Biol., September 1, 2006; 26(18): 6936 - 6949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Fostel, J. Dluzniewska, Y. Shimizu, B. J. Burbach, and E. J. Peterson ADAP is dispensable for NK cell development and function Int. Immunol., August 1, 2006; 18(8): 1305 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Olenchock, R. Guo, M. A. Silverman, J. N. Wu, J. H. Carpenter, G. A. Koretzky, and X.-P. Zhong Impaired degranulation but enhanced cytokine production after Fc{varepsilon}RI stimulation of diacylglycerol kinase {zeta}-deficient mast cells J. Exp. Med., June 12, 2006; 203(6): 1471 - 1480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Silverman, J. Shoag, J. Wu, and G. A. Koretzky Disruption of SLP-76 Interaction with Gads Inhibits Dynamic Clustering of SLP-76 and Fc{varepsilon}RI Signaling in Mast Cells. Mol. Cell. Biol., March 1, 2006; 26(5): 1826 - 1838. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
