In:
The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 116.1-116.1
Kurzfassung:
FcγRIIIa(CD16A) pairs with FcR-common γ-chain for surface expression and function. Since many functionally distinct immune receptors utilize γ-chains as signaling subunit, we hypothesized that elements for specificity in receptor signaling may be determined by the distinct FcγR cytoplasmic domains (CY). In silico analysis identified a PKC phosphorylation consensus motif within CD16A-CY; and in vitro kinase assays demonstrated that it is specifically phosphorylated by PKC. Non-phosphorylated CD16A is more effective at activation of the Gab2/PI3K pathway, leading to enhanced degranulation, while phosphorylated CD16A mediates a more robust calcium flux, tyrosine phosphorylation of Syk and pro-inflammatory cytokine production. S100A4, a specific protein binding partner for CD16A-CY, inhibits phosphorylation of CD16A-CY by PKC in vitro. Reduction of S100A4 levels in vivo enhanced receptor phosphorylation upon cross-linking. Taken together, we show that among IgG and IgA receptors, PKC-mediated phosphorylation of CD16A is specific and modulates distinct signaling pathways engaged by the receptor. Calcium activated binding of S100A4 to CD16A, promoted by the initial calcium flux and attenuating the phosphorylation of CY, may serve as a negative feedback on cytokine production pathways during sustained receptor engagement and favor a shift to degranulation, consistent with the importance of degranulation following conjugate formation between CD16A+ effector cells and target cells.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.186.Supp.116.1
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2011
ZDB Id:
1475085-5
