Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors

Autor: Janet Glassford, Arnold R. Pizzey, B. Thomas, Eric Lam, Gerry G. B. Klaus, Lolita Banerji, N. Shaun, Jeroen van der Sman
Rok vydání: 1999
Předmět:
Zdroj: European Journal of Immunology. 29:3380-3389
ISSN: 1521-4141
0014-2980
DOI: 10.1002/(sici)1521-4141(199910)29:10<3380::aid-immu3380>3.0.co;2-c
Popis: Since signals via CD40 and the B cell receptor are known to synergize to induce B cell activation, we have analyzed the pocket protein/E2F complexes in mouse B lymphocytes following stimulation by anti-IgM, anti-CD40, alone or together. We find that E2F4 and DP1 form the predominant E2F heterodimers in the G0 and G1 phases of the cell cycle, complexed with hypophosphorylated p130. During late G1 and S phase this complex is replaced by at least three different E2F complexes, one of which is an E2F complex containing p107 or pRB as well as two "free" E2F complexes consisting of E2F4/DP1 and E2F1-3/DP1. These effects were mirrored by the levels and phosphorylation status of the three pocket proteins. We also observed an increase in electrophoretic mobility of DP1 and E2F4 as B cells progressed from G0 into early G1, resulting from their dephosphorylation. This is known to correlate with a decrease in DNA binding capacity of these proteins and could also be important for derepression of genes negatively regulated through E2F sites in their promoters. These results therefore indicate that the pRB/E2F pathway integrates proliferative signals emanating from the sIgM and CD40 receptors.
Databáze: OpenAIRE
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