PDK1 nucleates T cell receptor-induced signaling complex for NF-B activation (Science, 308:114-118, 1 April 2005)

報告日期: 2005/10/11
報告時間: 17:10/18:00
報告學生: 莊懷佳
講評老師: 林以行
附件下載:

PDK1 Nucleates T cell Receptor-Induced Signaling Complex for NFkB Activation

Science. 2005, 308: 114-118.

演講者:莊懷佳                時間:941011日下午5:10

講評老師:林以行 老師         地點:602 Room

Signaling pathway of T cell receptor (TCR) through NFkB activation is important for T cell proliferation and activation in adaptive immune system. Previous studies indicated that several molecules such as phosphoinositide 3-kinase (PI3K), protein kinas C (PKC) and CARD11-Bcl10-MALT1 (BCM) complex are involved in NFkB activation under CD3/CD28 stimulation. PI3K pathway from the TCR cluster leads to the activation of kinase PKC, and PDK1 (3-phophoinositide-dependent kinase 1), which may subsequently activate NFkB. However, the critical role and sequence of these events transducing from TCR to NFkB remained to be clarified. Whether PDK1 activates NFkB through the activation and recruitment of PKC or CBM complex? Also, how the BCM complex initiates the activation of IKK complex? In order to solve these questions, the authors searched the interaction between these events in PDK-1 or CARD11 deficient T cells by co-immunoprecipitation and immunoflurescence analyses. The authors demonstrated that PDK1 phosphorylated and recruited PKC to lipid raft, and the active PKC continually activated and recruited IKK complex for NFkB activation. Furthermore, PDK1 aggregated CBM complex into the lipid raft after TCR stimulation by binding with CARD11. Therefore, the catalytic members of CBM complex, Bcl10-MALT, might activate IKK complex leading to NFkB activation. The authors established a more detailed model of TCR-induced signaling to NFkB activation. After TCR stimulation, PDK1 separately recruits PKC and CBM complex, the former following recruits IKK complex, which are activated by the latter. Both matters contributed to the activation of NFkB and transduction signals of T cell activation.

Reference

1. Nicolai S. C. van Oers and Z. J. Chen. Kinasing and clipping down the NFkB Trail. Science. 2005, 308: 65-66.

2. D. Wang, et al. CD3/CD28 costimulation-induced NF- B activation is mediated by recruitment of protein kinase C- , Bcl10, and I B kinase ß to the immunological synapse through CARMA1. Mol. Cell. Biol. 2004, 24: 164-171.