Identification of a Tumor Specific, Active-Site Mutation in Casein Kinase 1[alpha] by Chemical Proteomics

• Published in: PloS one Vol. 11; no. 3
• Main Authors: Okerberg, Eric S, Hainley, Anna, Brown, Heidi, Aban, Arwin, Alemayehu, Senait, Shih, Ann, Wu, Jane, Patricelli, Matthew P, Kozarich, John W, Nomanbhoy, Tyzoon, Rosenblum, Jonathan S
• Format: Journal Article
• Language: English
• Published: Public Library of Science 31.03.2016
• Subjects: Analysis; Gene mutation; Genetic aspects; Phosphotransferases; Proteomics; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152934

We describe the identification of a novel, tumor-specific missense mutation in the active site of casein kinase 1[alpha] (CSNK1A1) using activity-based proteomics. Matched normal and tumor colon samples were analyzed using an ATP acyl phosphate probe in a kinase-targeted LC-MS.sup.2 platform. An anomaly in the active-site peptide from CSNK1A1 was observed in a tumor sample that was consistent with an altered catalytic aspartic acid. Expression and analysis of the suspected mutant verified the presence of asparagine in the probe-labeled, active-site peptide for CSNK1A1. Genomic sequencing of the colon tumor samples confirmed the presence of a missense mutation in the catalytic aspartic acid of CSNK1A1 (GAC[right arrow]AAC). To our knowledge, the D163N mutation in CSNK1A1 is a newly defined mutation to the conserved, catalytic aspartic acid of a protein kinase and the first missense mutation identified using activity-based proteomics. The tumorigenic potential of this mutation remains to be determined.