Lck controls T cell activation by modifying p62

Lck transiently phosphorylates p62 at tyrosine 433 within 5 minutes of T cell receptor stimulation, which is associated with enhanced T cell activation.

• The phosphorylation of p62 by Lck inhibits TCR-induced autophagy.
• The p62-Y433F mutant shows increased association with LC3 and ULK1 complex components, enhancing autophagy.
• This mutant also suppresses NF-κB activation and IL-2 production by promoting Bcl10 autophagic degradation.
• Transient phosphorylation of p62 by Lck facilitates a shift from Bcl10-NF-κB signaling to autophagy during early TCR stimulation.

Simplified