TY - JOUR
T1 - Differential effects of B cell receptor and B cell receptor-FcγRIIB1 engagement on docking of Csk to GTPase-activating protein (GAP)-associated p62
AU - Vuica, Milena
AU - Desiderio, Stephen
AU - Schneck, Jonathan P.
PY - 1997/7/21
Y1 - 1997/7/21
N2 - The stimulatory and inhibitory pathways initiated by engagement of stimulatory receptors such as the B cell receptor for antigen (BCR) and inhibitory receptors such as Fcγ receptors of the IIB1 type (FcγRIIB1) intersect in ways that are poorly understood at the molecular level. Because the tyrosine kinase Csk is a potential negative regulator of lymphocyte activation, we examined the effects of BCR and FcγRIIB1 engagement on the binding of Csk to phosphotyrosine-containing proteins. Stimulation of a B lymphoma cell line, A20, with intact anti-IgG antibody induced a direct, SH2- mediated association between Csk and a 62-κD phosphotyrosine-containing protein that was identified as RasGTPase-activating protein-associated p62 (GAP-A.p62). In contrast, stimulation of A20 cells with anti-IgG F(ab')2 resulted in little increase in the association of Csk with GAP-A.p62. The effect of FcγRIIB1 engagement on this association was abolished by blockade of FcγRIIB1 with the monoclonal antibody 2.4G2. Furthermore, the increased association between Csk and GAP-A.p62 seen upon stimulation with intact anti- Ig was abrogated in the FcγRIIB1-deficient cell line IIA1.6 and recovered when FcγRIIB1 expression was restored by transfection. The differential effects of BCR and BCR-FcγRIIB1-mediated signaling on the phosphorylation of GAP-A.p62 and its association with Csk suggest that docking of Csk to GAP- A.p62 may function in the negative regulation of antigen receptor-mediated signals in B cells.
AB - The stimulatory and inhibitory pathways initiated by engagement of stimulatory receptors such as the B cell receptor for antigen (BCR) and inhibitory receptors such as Fcγ receptors of the IIB1 type (FcγRIIB1) intersect in ways that are poorly understood at the molecular level. Because the tyrosine kinase Csk is a potential negative regulator of lymphocyte activation, we examined the effects of BCR and FcγRIIB1 engagement on the binding of Csk to phosphotyrosine-containing proteins. Stimulation of a B lymphoma cell line, A20, with intact anti-IgG antibody induced a direct, SH2- mediated association between Csk and a 62-κD phosphotyrosine-containing protein that was identified as RasGTPase-activating protein-associated p62 (GAP-A.p62). In contrast, stimulation of A20 cells with anti-IgG F(ab')2 resulted in little increase in the association of Csk with GAP-A.p62. The effect of FcγRIIB1 engagement on this association was abolished by blockade of FcγRIIB1 with the monoclonal antibody 2.4G2. Furthermore, the increased association between Csk and GAP-A.p62 seen upon stimulation with intact anti- Ig was abrogated in the FcγRIIB1-deficient cell line IIA1.6 and recovered when FcγRIIB1 expression was restored by transfection. The differential effects of BCR and BCR-FcγRIIB1-mediated signaling on the phosphorylation of GAP-A.p62 and its association with Csk suggest that docking of Csk to GAP- A.p62 may function in the negative regulation of antigen receptor-mediated signals in B cells.
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U2 - 10.1084/jem.186.2.259
DO - 10.1084/jem.186.2.259
M3 - Article
C2 - 9221755
AN - SCOPUS:0030757853
SN - 0022-1007
VL - 186
SP - 259
EP - 267
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -