RT Journal Article
SR Electronic
T1 Quantitative proteomics identifies PTP1B as modulator of B cell antigen receptor signaling
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101084
DO 10.26508/lsa.202101084
VO 4
IS 11
A1 Schwarz, Jennifer J
A1 Grundmann, Lorenz
A1 Kokot, Thomas
A1 Kläsener, Kathrin
A1 Fotteler, Sandra
A1 Medgyesi, David
A1 Köhn, Maja
A1 Reth, Michael
A1 Warscheid, Bettina
YR 2021
UL http://www.life-science-alliance.org/content/4/11/e202101084.abstract
AB 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 activation. Through substrate trapping in combination with quantitative mass spectrometry, we identified 22 putative substrates or interactors of PTP1B. We validated Igα, CD22, PLCγ1/2, 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.