PMID- 10542198 OWN - NLM STAT- MEDLINE DCOM- 19991213 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 45 DP - 1999 Nov 5 TI - Rapid STAT phosphorylation via the B cell receptor. Modulatory role of CD19. PG - 31770-4 AB - 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 naive 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. FAU - Su, L AU - Su L AD - Department of Biology, University of California San Diego, La Jolla, California 92093-0322, USA. FAU - Rickert, R C AU - Rickert RC FAU - David, M AU - David M LA - eng GR - R01 CA080105/CA/NCI NIH HHS/United States GR - R01 CA080105-01/CA/NCI NIH HHS/United States GR - R01 CA080105-02/CA/NCI NIH HHS/United States GR - R01 CA080105-03/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Acute-Phase Proteins) RN - 0 (Antigens, CD19) RN - 0 (DNA-Binding Proteins) RN - 0 (Receptors, Antigen, B-Cell) RN - 0 (STAT1 Transcription Factor) RN - 0 (STAT1 protein, human) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (Trans-Activators) RN - 42HK56048U (Tyrosine) RN - 452VLY9402 (Serine) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Protein-Serine-Threonine Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinases) RN - EC 2.7.11.25 (MAP3K1 protein, human) SB - IM MH - Acute-Phase Proteins/*metabolism MH - Antigens, CD19/*metabolism MH - DNA-Binding Proteins/*metabolism MH - Humans MH - *MAP Kinase Kinase Kinase 1 MH - MAP Kinase Kinase Kinases/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation MH - *Protein-Serine-Threonine Kinases MH - Receptors, Antigen, B-Cell/*metabolism MH - STAT1 Transcription Factor MH - STAT3 Transcription Factor MH - Serine/metabolism MH - *Signal Transduction MH - Trans-Activators/*metabolism MH - Tyrosine/metabolism PMC - PMC2772110 MID - NIHMS145350 EDAT- 1999/11/05 00:00 MHDA- 1999/11/05 00:01 CRDT- 1999/11/05 00:00 PHST- 1999/11/05 00:00 [pubmed] PHST- 1999/11/05 00:01 [medline] PHST- 1999/11/05 00:00 [entrez] AID - 10.1074/jbc.274.45.31770 [doi] AID - S0021-9258(19)51486-7 [pii] PST - ppublish SO - J Biol Chem. 1999 Nov 5;274(45):31770-4. doi: 10.1074/jbc.274.45.31770.