title: Identification of a Tumor Specific, Active-Site Mutation in Casein Kinase 1α by Chemical Proteomics.
abstract: We describe the identification of a novel, tumor-specific missense mutation in the active site of casein kinase 1α (CSNK1A1) using activity-based proteomics. Matched normal and tumor colon samples were analyzed using an ATP acyl phosphate probe in a kinase-targeted LC-MS2 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→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.
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Okerberg
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Hainley
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Heidi
authors.initials: H
authors.lastname: Brown
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Arwin
authors.initials: A
authors.lastname: Aban
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Senait
authors.initials: S
authors.lastname: Alemayehu
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Ann
authors.initials: A
authors.lastname: Shih
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Jane
authors.initials: J
authors.lastname: Wu
authors.affiliation: Wellspring Biosciences LLC, La Jolla, CA, United States of America.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Patricelli
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Kozarich
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Tyzoon
authors.initials: T
authors.lastname: Nomanbhoy
authors.affiliation: ActivX Biosciences, Inc., La Jolla, CA, United States of America.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Rosenblum
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D048128:Casein Kinase Ialpha / Q000737:chemistry / Q000235:genetics*; D020134:Catalytic Domain; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D040901:Proteomics / Q000379:methods
chemical_list: D048128:Casein Kinase Ialpha