Antigen Receptor
NF-kB is a crucial target of signaling through both the T cell (A) and B cell (B) receptor complexes shown below. In this capacity, NF-kB has a vital role in the regulation of genes that influence the ability to initiate and sustain an adaptive immune response. Research in our laboratory has focused on two main areas - - the role of NF-kB in lymphocyte development - mechanisms whereby engagement of antigen receptors activates NF-kB In a recent study we demonstrate that 3-phosphoinositide dependent kinase 1 (PDK1) plays an essential role in this pathway by regulating the activation of PKCtheta and the signal-dependent recruitment of both PKCtheta and CARD11 to lipid rafts. PDK1-associated PKCtheta recruits the IKK complex, while PDK1-associated CARD11 recruits the Bcl-10/MALT1 complex, thereby allowing activation of IKK complex through Bcl-10/MALT1-dependent ubiquitination of NEMO. Hence PDK1 plays a unique role in nucleating the TCR-induced NF-kB activation.
 
Antigen Receptor signaling Publications
Lee, K.Y., et al., PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation. Science, 2005. 308(5718): p. 114-8.
Jimi, E. et al. Activation of NF-{kappa}B promotes the transition of large, CD43+ pre-B cells to small, CD43- pre-B cells. Int Immunol. 2005 May 20
Voll, R.E., et al., NF-kappa B activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development. Immunity, 2000. 13(5): p. 677-89.
Voll, R.E. and S. Ghosh, Role of NF-kappa B in T-lymphocyte development. Cold Spring Harb Symp Quant Biol, 1999. 64: p. 485-90.
Phillips, R.J. and S. Ghosh, Regulation of IkappaB beta in WEHI 231 mature B cells. Mol Cell Biol, 1997. 17(8): p. 4390-6.
Phillips, R.J., S. Gustafson, and S. Ghosh, Identification of a novel NF-kappaB p50-related protein in B lymphocytes. Mol Cell Biol, 1996. 16(12): p. 7089-97
Ghosh Lab