Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/13420
Title: Elucidating the role of Dok-3 in B cell receptor signaling using gene knockout mice
Authors: NG CHEE HOE
Keywords: B cell receptor, Dok-3, SHIP-1, negative regulator, gene knockout, immune response
Issue Date: 13-Nov-2007
Source: NG CHEE HOE (2007-11-13). Elucidating the role of Dok-3 in B cell receptor signaling using gene knockout mice. ScholarBank@NUS Repository.
Abstract: Dok-3 is a negative regulator of B cell receptor signaling. To date, the physiological function of Dok-3 is still unclear. We have generated the Dok-3-/- mice. Dok-3-/- mice have normal B cell population in the central and peripheral immune organs; exhibit elevated basal serum IgM but normal IgG1, IgG2a, IgG2b and IgG3; hyper-responsive towards T-independent antigens but showed comparable primary and secondary responses when challenged by a T-dependent antigen. Dok-3-/- B cells also hyper-proliferated and exhibited elevated magnitude of calcium flux in response to B cell receptor stimulation. We found that in Dok-3-/- B cells, SHIP1 was not activated optimally upon BCR stimulation, with reduced phosphorylation at tyrosine 1020. Dok-3-/- B cells also showed enhanced phosphorylation of JNK and p38; exhibited increased IkappaBalpha degradation accompanied by enhanced NFkappaB DNA binding. As such, all experiments pointed towards Dok-3 as a negative regulator of B cell receptor signaling.
URI: http://scholarbank.nus.edu.sg/handle/10635/13420
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