FCRL1-mediated ERK inhibition through adapter functions of SHIP-1 2935

Abstract Description FCRL1 is a tyrosine-phosphorylated receptor expressed on B cells beginning at the immature phase. FCRL1 has been shown to potentiate B cell receptor-driven calcium signaling and is important for thymus-independent B cell responses. Our previous studies have found that upon BCR stimulation, FCRL1 also negatively regulates ERK phosphorylation in a GRB2- dependent manner. Of the proteins associated with FCRL1, SHIP1 recruitment was observed to be GRB2-dependent. Examination of the recruitment of SHIP-1 to FCRL1 has revealed that SHIP-1 is recruited to FCRL1 through its C-terminal proline-rich region, presumably via one of the SH3 domains of GRB2. Furthermore, examination of ERK phosphorylation after BCR stimulation revealed that adapter functions of SHIP-1, mediated through its SH2 domain, are sufficient to produce the ERK-inhibitory effects of FCRL1, and that inositol phosphatase activity is not required for ERK regulation through FCRL1 and SHIP-1. This shows a novel role for SHIP-1 and FCRL1 in regulating B cell signaling cascades. Funding Sources NIH 1R15AI174170-01A1 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)