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. Author manuscript; available in PMC: 2011 Dec 1.
Published in final edited form as: Curr Opin Cell Biol. 2010 Dec;22(6):865–871. doi: 10.1016/j.ceb.2010.08.003

Figure 2.

Figure 2

Pathways involved in thymocyte development during the DP stage. The discrimination of MAPK pathways following TCR ligation results in different selection outcomes. Low-avidity TCR interactions with MHC-peptide (not shown) lead to positive selection, dependent on Erk1/2, whereas high-avidity interactions lead to negative selection, dependent on the recruitment of Grb2/Sos and activation of p38 and Jnk. Negative selecting ligands also result in ERK5 and MINK activation. The convergence of these pathways leads to activation of the Nur77 family and Bim death effectors. (Dotted lines represent potential signaling outcomes). Bim antagonizes Bcl-2 to allow Bax and Bak to effect mitochondrial dysfunction, while Nur77 family members have been shown to turn Bcl-2 into an apotosis promoting protein at the mitochondria. Mcl-1 and Bcl-xL antagonize the function of Bax/Bak, but in the absence of TCR signals, cannot protect cells from apoptosis. TRAIL is induced by Nur77, although the role of this DR in thymocyte apoptosis remains to be fully clarified.