APKC: the Kinase that Phosphorylates Cell Polarity.

Yang Hong

doi:10.12688/f1000research.14427.1

Abstract

Establishing and maintaining cell polarity are dynamic processes that necessitate complicated but highly regulated protein interactions. Phosphorylation is a powerful mechanism for cells to control the function and subcellular localization of a target protein, and multiple kinases have played critical roles in cell polarity. Among them, atypical protein kinase C (aPKC) is likely the most studied kinase in cell polarity and has the largest number of downstream substrates characterized so far. More than half of the polarity proteins that are essential for regulating cell polarity have been identified as aPKC substrates. This review covers mainly studies of aPKC in regulating anterior-posterior polarity in the worm one-cell embryo and apical-basal polarity in epithelial cells and asymmetrically dividing cells (for example, Drosophila neuroblasts). We will go through aPKC target proteins in cell polarity and discuss various mechanisms by which aPKC phosphorylation controls their subcellular localizations and biological functions. We will also review the recent progress in determining the detailed molecular mechanisms in spatial and temporal control of aPKC subcellular localization and kinase activity during cell polarization.

Highlights

Atypical protein kinase C, classic PKC, and novel PKC are the three major PKC subfamilies[1]
The Ohno group, who were at the time searching for Atypical protein kinase C (aPKC)-interacting proteins, identified a mammalian protein they termed ASIP, which turned out to be the homologue of Caenorhabditis elegans polarity protein Par-32
Recent studies showed that the CR3 domain carrying the aPKC phosphorylation site of Baz contains two flanking “arms” that bind to the kinase domain of aPKC and inhibit its kinase activity[47]

Summary

Introduction

Atypical protein kinase C (aPKC), classic PKC (cPKC), and novel PKC (nPKC) are the three major PKC subfamilies[1]. A recurring theme of aPKC phosphorylation-dependent regulation is that phosphorylation by aPKC often inhibits target proteins from localizing to plasma membrane (PM) or cell cortex allowing apically or anteriorly localized aPKC to exclude these target proteins from opposite PM/cortical domains during the process of establishing and maintaining polarity. Mechanisms underlying this phosphorylation-dependent inhibition of PM/ cortical localization of Lgl, Numb, and Mir had long been puzzling, and only recently has it become clear that Lgl, Numb, and Mir are all direct PM-binding proteins containing so-called polybasic ( known as “basic-hydrophobic”) domains which are highly positively charged because of the abundance of Arg and Lys residues[14,15].

Results

Conclusion