TY - JOUR
T1 - Differential requirement for adapter proteins Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa and adhesion- and degranulation-promoting adapter protein in FcεRI signaling and mast cell function
AU - Wu, Jennifer N.
AU - Jordan, Martha S.
AU - Silverman, Michael A.
AU - Peterson, Erik J.
AU - Koretzky, Gary A.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2004/6/1
Y1 - 2004/6/1
N2 - The adapter molecule Src homology 2 (SH2) domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is essential for FcεRI-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 FcεRI-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 FcεRI-induced degranulation. Surprisingly, we found that mast cells lacking ADAP expression demonstrate no defects in FcεRI-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.
AB - The adapter molecule Src homology 2 (SH2) domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is essential for FcεRI-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 FcεRI-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 FcεRI-induced degranulation. Surprisingly, we found that mast cells lacking ADAP expression demonstrate no defects in FcεRI-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.
UR - http://www.scopus.com/inward/record.url?scp=2442700314&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442700314&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.172.11.6768
DO - 10.4049/jimmunol.172.11.6768
M3 - Article
C2 - 15153494
AN - SCOPUS:2442700314
SN - 0022-1767
VL - 172
SP - 6768
EP - 6774
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -