Myc oncoproteins are phosphorylated by casein kinase II.

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Abstract
Casein kinase II (CK‐II) is a ubiquitous protein kinase, localized to both nucleus and cytoplasm, with strong specificity for serine residues positioned within clusters of acidic amino acids. We have found that a number of nuclear oncoproteins share a CK‐II phosphorylation sequence motif, including Myc, Myb, Fos, E1a and SV40 T antigen. In this paper we show that cellular myc‐encoded proteins, derived from avian and human cells, can serve as substrates for phosphorylation by purified CK‐II in vitro and that this phosphorylation is reversible. One‐ and two‐dimensional mapping experiments demonstrate that the major phosphopeptides from in vivo phosphorylated Myc correspond to the phosphopeptides produced from Myc phosphorylated in vitro by CK‐II. In addition, synthetic peptides with sequences corresponding to putative CK‐II phosphorylation sites in Myc are subject to multiple, highly efficient phosphorylations by CK‐II, and can act as competitive inhibitors of CK‐II phosphorylation of Myc in vitro. We have used such peptides to map the phosphorylated regions in Myc and have located major CK‐II phosphorylations within the central highly acidic domain and within a region proximal to the C terminus. Our results, along with previous studies on myc deletion mutants, show that Myc is phosphorylated by CK‐II, or a kinase with similar specificity, in regions of functional importance. Since CK‐II can be rapidly activated after mitogen treatment we postulate that CK‐II mediated phosphorylation of Myc plays a role in signal transduction to the nucleus.