Exploring the role of casein kinase 1α splice variants across cancer cell lines

Casein kinase 1 alpha (CK1 alpha) is a serine/threonine protein kinase that acts in various cellular processes affecting cell division and signal transduction. CK1 alpha is present as multiple splice variants that are distinguished by the presence or absence of a long insert (L -insert) and a short carboxyl -terminal insert (S -insert). When overexpressed, zebrafish CK1 alpha splice variants exhibit different biological properties, such as subcellular localization and catalytic activity. However, whether endogenous, alternatively spliced CK1 alpha gene products also differ in their biological functions has yet to be elucidated. Here, we identify a panel of splice variant specific CK1 alpha antibodies and use them to show that four CK1 alpha splice variants are expressed in mammals. We subsequently show that the relative abundance of CK1 alpha splice variants varies across distinct mouse tissues and between various cancer cell lines. Furthermore, we identify pathways whose expression is noticeably altered in cell lines enriched with select splice variants of CK1 alpha. Finally, we show that the S -insert of CK1 alpha promotes the growth of HCT 116 cells as cells engineered to lack the S -insert display decreased cell growth. Together, we provide tools and methods to identify individual CK1 alpha splice variants, which we use to begin to uncover the differential biological properties driven by specific splice variants of mammalian CK1 alpha.