Diacylglycerol Signaling

Chapter 10
Atypical PKCs, NF-kB, and Inflammation
Maria T. Diaz-Meco and Jorge Moscat
Abstract Complex biological processes, such as inflammation and cancer, rely on
the crosstalk and activation of distinct cellular networks that control gene expression.
Central to this process is the transcription factor NF-κB. In this chapter,
we focus on the role of the atypical protein kinase C (PKC) isoforms (aPKC) in
inflammation and cancer through the activation of this transcription factor in vivo.
The aPKCs are key members of a network of kinases, adapters and regulators, such
as p62 and Par-4, which confer functional plasticity and specificity to this critical
pathway. Here, we summarize the molecular mechanisms that govern that network,
learnt from the knock-out mouse models, to unravel its role and function in vivo.
Keywords aPKC • PKCζ • PKCι • p62 • Sequestosome • Par-4 • NF-κB • Inflammation
• Cancer
10.1 Introduction
The atypical protein kinase C (aPKC) subfamily of kinases is composed of two
members, PKCz and PKCl/i. PKCl is the mouse homolog of the human PKCi.
The two aPKC isoforms are highly related, sharing an overall amino acid identity
of 72% (Nishizuka 1995). The conservation in their sequences is most striking in
the catalytic domain, which is also conserved among other PKC isotypes that
belong to the classical and novel subfamilies. In contrast, the regulatory domain of
the aPKC subfamily diverts from other members of the PKC family; it has only one
zinc finger, whereas the other PKCs have two (Nishizuka 1995). Through the zincfinger
domain, the aPKCs bind Par-4, a negative regulator of their enzymatic activity.
M.T. Diaz-Meco (*) and J. Moscat
Department of Cancer and Cell Biology, University of Cincinnati College of Medicine,
3125 Eden Ave, Cincinnati, OH 45267, USA
e-mail: maria.diazmeco@uc.edu
M.G. Kazanietz (ed.), Protein Kinase C in Cancer Signaling and Therapy,
Current Cancer Research, DOI 10.1007/978-1-60761-543-9_10,
© Springer Science+Business Media, LLC 2010
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