Bi K, Tanaka Y, Coudronniere N, Sugie K, Hong S, van Stipdonk M J, Altman A
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Nat Immunol. 2001 Jun;2(6):556-63. doi: 10.1038/88765.
Protein kinase C-theta (PKC-theta) is essential for mature T cell activation; however, the mechanism by which it is recruited to the TCR signaling machinery is unknown. Here we show that T cell stimulation by antibodies or peptide-major histocompatibility complex (MHC) induces translocation of PKC-theta 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-straight theta catalytic fragment did not partition into rafts or activate the transcription factor NF-kappa B, although addition of a Lck-derived raft-localization sequence restored these functions. Thus, physiological T cell activation translocates PKC-theta to rafts, which localize to the T cell synapse; this PKC-theta translocation is important for its function.
蛋白激酶C-θ(PKC-θ)对于成熟T细胞的激活至关重要;然而,其被招募至TCR信号传导机制的具体机制尚不清楚。在此我们表明,抗体或肽-主要组织相容性复合体(MHC)对T细胞的刺激会诱导PKC-θ转位至膜脂筏,而膜脂筏定位于免疫突触。脂筏转位由PKC-θ调节结构域介导,且需要Lck而非ZAP-70。此外,PKC-θ在脂筏中与Lck相关联。一个分离的PKC-θ催化片段不会分配至脂筏或激活转录因子NF-κB,尽管添加一个源自Lck的脂筏定位序列可恢复这些功能。因此,生理性T细胞激活会使PKC-θ转位至定位于T细胞突触的脂筏;这种PKC-θ转位对其功能很重要。