Antigen-induced translocation of PKC-theta to membrane rafts is required for T cell activation

Protein kinase C-theta (PKC-theta) is essential for mature T cell activatio n; however, the mechanism by which it is recruited to the TCR signaling mac hinery is unknown. Here we show that T cell stimulation by antibodies or pe ptide-major histocompatibility complex (MHC) induces translocation of PKC-Q to membrane lipid rafts, which localize to the immunological synapse. Raft translocation was mediated by the PKC-theta regulatory domain and required Lck but not ZAP-70. In addition, PKC-theta was associated with Lck in the rafts,An isolated PKC-theta catalytic fragment did not partition into rafts or activate the transcription factor NF-kappaB, although addition of a Lck -derived raft-localization sequence restored these functions. Thus, physiol ogical T cell activation translocates PKC-theta to rafts, which localize to the T cell synapse; this PKC-theta translocation is important for its func tion.