CD19 cytoplasmic tyrosines, their binding partners and downstream signaling: An in vitro study.

摘要

CD19 is an important coreceptor on B cells which becomes phosphorylated on tyrosine after stimulation. Cytosolic Src Homology 2 (SH2) containing proteins then bind to CD19 phosphotyrosines and initiate downstream signaling pathways. Using mutagenesis, the role of various CD19 tyrosines in downstream Ca 2+ and extracellular signal-regulated kinase 2 (ERK2) signaling was determined in the Daudi B cell line. These studies indicate that a chimera with only four of nine tyrosines (330, 360, 391, and 421) could fully reconstitute signaling in Daudi cells in the context of wild type CD19. In addition to the known association of Vav with tyrosine (Y) 391 and phosphatidylinositol 3-kinase (PI3K) with Y482 and 513, new associations were discovered using coimmunoprecipitations and peptide precipitations, including Vav with Y421, phospholipase C (PLC)-γ2 with Y391, and 421, and Grb2/Sos with Y330.