Sci. Signal., 17 September 2013
Impairing Cell PolarityEpithelial 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 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 PKC to two substrates that are involved in cell polarization, and an epithelial cell line expressing a form of PKC 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.
Citation: M. Linch, M. Sanz-Garcia, E. Soriano, Y. Zhang, P. Riou, C. Rosse, A. Cameron, P. Knowles, A. Purkiss, S. Kjaer, N. Q. McDonald, P. J. Parker, A Cancer-Associated Mutation in Atypical Protein Kinase C Occurs in a Substrate-Specific Recruitment Motif. Sci. Signal. 6, ra82 (2013).
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