Rapid STAT phosphorylation via the B cell receptor - Modulatory role of CD19

Department of Biology, University of California San Diego, La Jolla, California 92093-0322, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 12/1999; 274(45):31770-4. DOI: 10.1074/jbc.274.45.31770
Source: PubMed


Engagement of the B cell receptor (BCR) initiates multiple signaling cascades which mediate different biological responses, depending on the stage of B cell differentiation, antigen binding affinity, and duration of stimulation. Aggregation of co-receptors such as CD19 with the antigen receptor has been suggested to modulate the signals necessary for the development and functioning of the humoral immune system. In this study, we demonstrate that engagement of the antigen receptor on peripheral blood B cells, but not naïve splenic B lymphocytes, leads to rapid phosphorylation of signal transducers and activators of transcription 1 (STAT1) on Tyr-701 and Ser-727. Interestingly, phosphorylation on tyrosine diminished with increased stimulation, whereas serine phosphorylation correlated directly with the level of BCR cross-linking. In contrast, phosphorylation of STAT3 occurs exclusively on serine and is sensitive to inhibitors of the PI3-kinase and the ERK1/2 pathways. Finally, we show that co-ligation of CD19 with the BCR results in increased tyrosine phosphorylation of STAT1 relative to BCR cross-linking alone, establishing CD19 as a positive modulator of BCR-mediated STAT activation.

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Available from: Michael David, Mar 17, 2015
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    • "In contrast, when STAT3-Ser phosphorylation is induced by treatment with IL-6 or IFN-alpha, phosphorylation is sensitive to a broad spectrum kinase inhibitor, H7 (Chung et al., 1997; Ng and Cantrell, 1997; Stephens et al., 1998; Su et al., 1999; Decker and Kovarik, 2000). Adding to the complexity of STAT- Ser phosphorylation regulation, multiple pathways activated by the same receptor impinge upon different STAT-Ser phosphorylations , adding to the complexity, as well as the utility, of STAT3 in regulating discrete biological processes (Kovarik et al., 1999; Lim and Cao, 1999; Decker and Kovarik, 2000). "
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