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Griffith, A. A.

Publications and source records attributed to Griffith, A. A..

2 recordsLinked to original sources

Mouse primary T cell phosphotyrosine proteomics enabled by BOOST

The Broad Spectrum Optimization of Selective Triggering (BOOST) approach was recently developed to increase the quantitative depth of the tyrosine phosphoproteome by mass spectrometry-based proteomics. While BOOST has been demonstrated in the Jurkat T cell line, it has not been demonstrated in scarce mice primary T cells. Here, we show the first phosphotyrosine proteomics experiment performed in mice primary T cells using BOOST. We identify and precisely quantify more than 2,000 unique pTyr sites from more than 3,000 unique pTyr peptide PSMs using only 1 mg of protein from T cell receptor-stimulated primary T cells from mice. We further reveal the importance of the phase-constrained spectrum deconvolution method ({Phi}SDM) parameter on Orbitrap instruments that, when disabled, enhances quantitation depth, accuracy, and precision in low-abundance samples. Using samples with contrived ratios, we find that disabling {Phi}SDM allows for up to a two-fold increase in the number of statistically significant intensity ratios detected while enabling {Phi}SDM degrades quantitation, especially in low-abundance samples. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/491817v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@4a2742org.highwire.dtl.DTLVardef@57645borg.highwire.dtl.DTLVardef@17dbfacorg.highwire.dtl.DTLVardef@b2df00_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

SILAC phosphoproteomics reveals unique signaling circuits in CAR-T cells and the inhibition of B cell-activating phosphorylation in target cells

Chimeric antigen receptor (CAR) is a single-pass transmembrane receptor designed to specifically target and eliminate cancers. While CARs prove highly efficacious against B cell malignancies, the intracellular signaling events which promote CAR T cell activity remain elusive. To gain further insight into both CAR T cell signaling and the potential signaling response of cells targeted by CAR, we analyzed phosphopeptides captured by two separate phopshoenrichment strategies from third generation CD19-CAR T cells cocultured with SILAC labeled Raji B cells by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Here, we report that CD19-CAR T cells upregulated several key phosphorylation events also observed in canonical T cell receptor (TCR) signaling while Raji B cells exhibited a significant decrease in B cell receptor-signaling related phosphorylation events in response to coculture. Our data suggest that CD19-CAR stimulation activates a mixture of unique CD19-CAR-specific signaling pathways and canonical TCR signaling while global phosphorylation in Raji B cells is reduced after association with the CD19-CAR T cells.

cell biology↗