The Tyrosine Phosphatase CD148 is Excluded from the Immunologic Synapse and Down-regulates Prolonged T Cell Signaling

?? Joseph Lin and Arthur Weis, 2011. Originally published in The Journal of Cell Biology. doi: 10.1083/jcb.200303040.CD148 is a receptor-like protein tyrosine phosphatase\ud up-regulated on T cells after T cell receptor\ud (TCR) stimulation. To examine the physiologic role\ud of CD148 in TCR signaling, we used an inducible CD148-\ud expressing Jurkat T cell clone. Expression of CD148 inhibits\ud NFAT (nuclear factor of activated T cells) activation induced\ud by soluble anti-TCR antibody, but not by antigen-presenting\ud cells (APCs) loaded with staphylococcal enterotoxin superantigen\ud (SAg) or immobilized anti-TCR antibody. Immunofluorescence\ud microscopy revealed that the extracellular\ud C\ud domain of CD148 mediates its exclusion from the immunologic\ud synapse, sequestering it from potential substrates.\ud Targeting of the CD148 phosphatase domain to the immunologic\ud synapse potently inhibited NFAT activation by all\ud means of triggering through the TCR. These data lead us to\ud propose a model where CD148 function is regulated in\ud part by exclusion from substrates in the immunologic synapse.\ud Upon T cell???APC disengagement, CD148 can then\ud access and dephosphorylate substrates to down-regulate\ud prolongation of signaling.This work was supported in part by research funds from the state of California