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. Author manuscript; available in PMC: 2010 Sep 17.
Published in final edited form as: Sci Signal. 2010 Aug 3;3(133):ra59. doi: 10.1126/scisignal.2000976

Fig. 10.

Fig. 10

Proposed model for the Duox1-mediated regulation of TCR signaling. TCR stimulation leads, through the activation of several protein kinases, to the activation of PLC-γ1. The resulting hydrolysis of phosphatidylinositol-4,5-bisphosphate to diacylglycerol and IP3 leads to the binding of IP3 to IP3R1, which causes the release of Ca2+ from the ER. Duox1 that is associated with IP3R1 is activated by the Ca2+ that is released from ER and also through phosphorylation, potentially by PKC. Duox1-mediated production of ROS inactivates the SHP-2 protein that is associated with Gab2 in proximity to complexes of TCR, Lck, and ZAP-70. Oxidative inactivation of SHP-2 relieves the inhibitory effects of SHP-2 activity on ZAP-70 and promotes further TCR signaling, such as the activation of ERK and the influx of extracellular Ca2+.