Src-family kinases negatively regulate NFAT signaling in resting human T cells
Fig 8
Proposed model for the role of active SFKs in resting human T cells.
In resting human T cells, a pool of active Src-family kinases (SFKs) phosphorylates the Csk-binding protein (Cbp). Csk bound to the phosphorylated Cbp phosphorylates the majority of SFKs at the inhibitory C-terminal tyrosine. SFKs phosphorylated at the C-terminal inhibitory tyrosine are enzymatically inactive and cannot mediate proximal T cell receptor (TCR) signaling in absence of TCR stimulation. In addition, this active pool of SFKs also prevents aberrant NFAT1 activation and negatively regulates NFAT1-mediated distal TCR signaling in resting human T cells by suppressing calcineurin activity. Together, negative regulation of both proximal and distal TCR signaling by active SFKs contribute to maintain T cells in a quiescent state in absence of TCR stimulation.