Proteomics

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Quantitative Proteomics Identifies Protein Tyrosine Phosphatase 1B as Modulator of B Cell Antigen Receptor Signaling


ABSTRACT: B cell antigen receptor (BCR) signaling is initiated by protein kinases and limited by counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. We here used the B cell line Ramos to identify and quantify human B cell signaling components. Specifically, a protein tyrosine phosphatase profiling revealed a high expression of the protein tyrosine phosphatase 1B (PTP1B) in Ramos and human naive B cells. The loss of PTP1B leads to increased B cell activation. Through substrate trapping in combination with quantitative mass spectrometry, we identified 22 putative substrates or interactors of PTP1B. We validated Igalpha, CD22, PLCgamma1/2, CBL, BCAP and APLP2 as specific substrates of PTP1B in Ramos B cells. The tyrosine kinase BTK and the two adaptor proteins GRB2 and VAV1 were identified as direct binding partners and potential substrates of PTP1B. We showed that PTP1B dephosphorylates the inhibitory receptor protein CD22 at phosphotyrosine 807. We conclude that PTP1B negatively modulates BCR signaling by dephosphorylating distinct phosphotyrosines in B cell specific receptor proteins and various downstream signaling components.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Culture

SUBMITTER: Jennifer Schwarz  

LAB HEAD: Bettina Warscheid

PROVIDER: PXD024037 | Pride | 2022-02-16

REPOSITORIES: Pride

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Quantitative proteomics identifies PTP1B as modulator of B cell antigen receptor signaling.

Schwarz Jennifer J JJ   Grundmann Lorenz L   Kokot Thomas T   Kläsener Kathrin K   Fotteler Sandra S   Medgyesi David D   Köhn Maja M   Reth Michael M   Warscheid Bettina B  

Life science alliance 20210915 11


B cell antigen receptor (BCR) signaling is initiated by protein kinases and limited by counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. Here, we used the B cell line Ramos to identify and quantify human B cell signaling components. Specifically, a protein tyrosine phosphatase profiling revealed a high expression of the protein tyrosine phosphatase 1B (PTP1B) in Ramos and human naïve B cells. The loss of PTP1B leads to increased B cell activati  ...[more]

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