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10.1038/s41598-018-22544-x

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suck abstract from ncbi


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pmid29523808      Sci+Rep 2018 ; 8 (ä): ä
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  • Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells #MMPMID29523808
  • Vanshylla K; Bartsch C; Hitzing C; Krümpelmann L; Wienands J; Engels N
  • Sci Rep 2018[]; 8 (ä): ä PMID29523808show ga
  • The B cell antigen receptor (BCR) employs enzymatically inactive adaptor proteins to facilitate activation of intracellular signaling pathways. In animal model systems, adaptor proteins of the growth factor receptor-bound 2 (Grb2) family have been shown to serve critical functions in lymphocytes. However, the roles of Grb2 and the Grb2-related adaptor protein (GRAP) in human B lymphocytes remain unclear. Using TALEN-mediated gene targeting, we show that in human B cells Grb2 and GRAP amplify signaling by the immunoglobulin tail tyrosine (ITT) motif of mIgE-containing BCRs and furthermore connect immunoreceptor tyrosine-based activation motif (ITAM) signaling to activation of the Ras-controlled Erk MAP kinase pathway. In contrast to mouse B cells, BCR-induced activation of Erk in human B cells is largely independent of phospholipase C-? activity and diacylglycerol-responsive members of Ras guanine nucleotide releasing proteins. Together, our results demonstrate that Grb2 family adaptors are critical regulators of ITAM and ITT signaling in naïve and IgE-switched human B cells.
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