Review
Cell Death and Differentiation (2006) 13, 702–711. doi:10.1038/sj.cdd.4401823; published online 2 December 2005
PKC
at the crossroad of NF-
B and Jak1/Stat6 signaling pathways
Edited by G Kroemer
J Moscat1, P Rennert2 and M T Diaz-Meco1
- 1Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain
- 2Biogen-Idec, 14 Cambridge Center, Cambridge, MA 02142, USA
Correspondence: J Moscat, Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Canto Blanco, 28049 Madrid, Spain. Tel: +34 914978039; Fax: +34 917616184; E-mail: jmoscat@cbm.uam.es
Received 19 September 2005; Revised 24 October 2005; Accepted 25 October 2005; Published online 2 December 2005.
Abstract
The atypical protein kinase C (PKC) isoforms (aPKC) have been implicated in the regulation of a number of essential signaling events. Early studies using dominant-negative mutants suggested that they are important intermediaries in the activation of the canonical nuclear factor (NF)-
B pathway. More recent data using knockout mice genetically demonstrate that in fact the PKC
isoform is essential for the adequate activation of this cascade both upstream and downstream the IB kinase complex. In this review, we summarize the mechanistic details whereby the aPKC pathway regulates important cellular functions and how this is achieved by the ability of these kinases to interact with different protein regulators and adapters, as well as to impinge in NF-B-independent signaling cascades such as the Janus kinase-1/signal transducer and activator of transcription 6 system, which plays a critical role in T-cell-mediated hepatitis and asthma.
Keywords:
atypical PKCs, NF-B, apoptosis, inflammation, cancer, p62/Sequestosome, Par4, Th2 polarization, asthma
Abbreviations:
BCR, B-cell receptor; CBP, CREB-binding protein; COPD, chronic obstructive pulmonary disease; CREB, cyclic AMP-binding protein; Dif, dorsal-related immunity factor; EGF, epidermal growth factor; ERK, extracellular responsive kinase; IFN-
, interferon-; Ig, immunoglobulin; IB, inhibitor of B; IKK, IB kinase; IL, interleukin; Jak1, Janus kinase-1; JNK, Jun kinase; KID, kinase-inducible transactivation domain; LPS, lipopolysaccharide; LT, lymphotoxin; MEK, MAPK/ERK kinase; MSK-1, mitogen- and stress-activated protein kinase 1; NF-AT, nuclear factor of activated T cells; NF-B, nuclear factor-B; Par-4, prostate androgen responsive-4; Par-6, partitioning defective-6; PI-PLC, phosphoinositide-specific phospholipase C; PKA, protein kinase A; PKC, protein kinase C; PLC, phospholipase C; RANK-L, receptor activator of NF-B-ligand; RIP, receptor-interacting protein; Stat6, signal transducer and activator of transcription 6; TCR, T-cell receptor; Th, T helper; TNF
, tumor necrosis factor ; TRAF, TNF receptor-associated factor; UBA, ubiquitin associated; XIAP, X-linked mammalian inhibitor of apoptosis protein
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