FIGURE 7.

Model of TCR signaling attenuation by SLP-76 ubiquitination. Following stimulation, SLP-76 is tyrosine-phosphorylated and activated. Activation of SLP-76 initiates the formation of the SLP-76-interacting protein complex, leading to activation of downstream TCR signaling. HPK1 is also activated by interacting with SLP-76. Activated HPK1 then induces phosphorylation of SLP-76 Ser-376, resulting in the binding of 14-3-3. 14-3-3 dimers recruit a putative E3 ubiquitin (Ub) ligase to SLP-76; the putative E3 ligase in turn induces SLP-76 ubiquitination at Lys-30, leading to degradation of activated SLP-76 and subsequent attenuation of TCR signaling.