Research ArticleCell Biology

A Cancer-Associated Mutation in Atypical Protein Kinase Cι Occurs in a Substrate-Specific Recruitment Motif

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Science Signaling  17 Sep 2013:
Vol. 6, Issue 293, pp. ra82
DOI: 10.1126/scisignal.2004068

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Impairing Cell Polarity

Epithelial cells simultaneously interact with both the external and internal environment. To perform their function as barriers, epithelial cells are polarized, meaning that they are asymmetric in shape and in the distribution of intracellular components. Epithelial cells in tumors often show loss of polarity. Linch et al. identified a 4–amino acid motif in the ι isoform of atypical protein kinase C (PKC), a kinase that promotes cell polarity through phosphorylation of various substrates. Mutations in this motif impaired the binding of PKCι to two substrates that are involved in cell polarization, and an epithelial cell line expressing a form of PKCι with mutations in this motif formed improperly polarized epithelial structures. Somatic mutations in this motif were detected in human cancers of various types. Thus, this study provides a mechanism by which these mutations contribute to the disease.

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