2009年1月4日 · CD28 facilitated NF-κB activation by regulating recruitment and phosphorylation of PDK1, which are necessary for efficient binding of PDK1 to protein kinase C-θ and the adaptor CARMA1 and...

We show here that phosphoinositide-dependent kinase 1 (PDK1) is essential for integrating the TCR and CD28 signals. After we deleted PDK1 from T cells, TCR-CD28 signals were unable to induce activation of NF-kappaB or phosphorylation of protein kinase C-theta, although T cell survival and pathways dependent on the kinases p38 and Jnk or the ...

CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis.

We demonstrated here that phosphoinositide-dependent kinase 1 (PDK1) plays an essential role in integrating TCR and CD28 signals. Upon deletion of PDK1 in T cells, TCR-CD28 signals failed to induce NF-κB activation or protein kinase C θ (PKC-θ) phosphorylation, although T cell survival and pathways dependent on p38 and Jnk kinases or ...

2006年7月7日 · CD3/CD28 stimulation induces the PDK1-mediated phosphorylation of PKA, with PDK1 and PKA shown to physically interact and partially colocalize at the immune synapse. Expression of the PDK1-KH molecule in D10 T cells was shown in this report to potently activate the IL-4 promoter via the NFAT P1 element.

2003年7月1日 · CD28 shares with ICOS an ability to amplify the production of T H 2 cytokines 118, which indicates that their shared activation of the PI3K–PDK1–PKB pathway might regulate these T H 2 cytokines.

2005年4月1日 · To assess the role of PDK1 in TCR signaling through PKCθ, we tested whether endogenous PDK1 interacted with PKCθ in primary T cells that were either unstimulated or stimulated with antibodies against CD3 and CD28 (anti-CD3 anti-CD28).

2013年2月5日 · Phosphoinositide-dependent kinase 1 (PDK1) plays an important role in integrating the T cell antigen receptor (TCR) and CD28 signals to achieve efficient NF-κB activation. PDK1 is also an important regulator of T cell development, mediating pre-TCR induced proliferation signals.

2006年7月10日 · Phosphorylation of the critical PKA threonine residue is stimulated by engagement of TCR/CD28 via a PDK1-dependent mechanism. These findings together define a pathway linking the kinases PDK1 and PKA in the induction of the Th2 cytokine IL-4.

Strong NF-κB activation requires ligation of both the CD28 co-receptor and TCR. PDK1 acts as a scaffold by binding both PKCθ and CARMA1 and is therefore essential for signaling to NF-κB. Here, we demonstrate the importance of PDK1 threonine (Thr)-513 phosphorylation in regulating the intermolecular organization of PDK1 homodimers.