Kinase Subfamily PKCi
Kinase Classification: Group AGC: Family PKC: Subfamily PKCi
PKCi is the 'atypical' Protein Kinase C subfamily, also known as aPKC
Evolution
PKCi are found through the animal kingdom, with two vertbebrate members, PKCi and PKCz (iota and zeta), and single members in Drosophila (aPKC) and C. elegans (pkc-3)
Domain Structure
PKCi have a PB1 domain followed by C1, kinase and pkinase_c domains. The PB1 domain is unique to this subfamily, and it lacks the C2 domain found in other PKC. It is activated by protein-protein interactions mediated by the PB1 domain, and is not responsive to DAG or Ca++, as are other PKCs.
Functions
PKCi/aPKC is part of the par complex that regulates cell polarity, in mammals, flies, and nematodes. The par complex consists of an aPKC, Par3 and Par6, and they function in, asymmetrical cell division (C. elegans embryo and Drosophila neuroblasts), apico-basal cell polarity, and mammalian neuronal polarity.
Par3 (par-3/Bazooka/PARD3A/B) binds to tight junctions, and to Par6, while Par6 (par-6, PARD6A/B/G, binds to aPKC via their shared PB1 domains. Par6 also recruits the small GTPases cdc42 or rac to the complex, which causes activation of aPKC kinase function.
The crumbs complex is another apical polarity complex which is regulated by the par complex. Par6 binds to Crumbs and aPKC phosphorylates it.
Mammalian PKCz has a brain-specific isoform, sometimes called PKMz, that lacks the regulatory N-terminus and is constitutively active. It is believe to be involved in long term potentiation [1].
