PKCzeta at the crossroad of NF-kappaB and Jak1/Stat6 signaling pathways.
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)-kappaB pathway. More recent data using knockout mice genetically demonstrate that in fact the PKCzeta isoform is essential for the adequate activation of this cascade both upstream and downstream the IkappaB 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-kappaB-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.
Moscat
J
J
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. jmoscat@cbm.uam.es
Rennert
P
P
Diaz-Meco
M T
MT
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004330:Drosophila; D007109:Immunity; D015847:Interleukin-4 / Q000494:pharmacology; D053613:Janus Kinase 1; D008099:Liver / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018418:Th2 Cells / Q000378:metabolism; D015533:Transcriptional Activation; D000099221:Protein Kinase C zeta
D015847:Interleukin-4; D053613:Janus Kinase 1; D016328:NF-kappa B; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D050800:STAT6 Transcription Factor; D000099221:Protein Kinase C zeta; C507905:Jak1 protein, mouse