Myc oncoproteins are phosphorylated by casein kinase II - PubMed (original) (raw)
Myc oncoproteins are phosphorylated by casein kinase II
B Lüscher et al. EMBO J. 1989 Apr.
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.
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References
- Proc Natl Acad Sci U S A. 1987 Dec;84(24):8834-8 - PubMed
- J Biol Chem. 1988 Nov 5;263(31):15872-5 - PubMed
- Oncogene. 1987 May;1(2):97-109 - PubMed
- J Virol. 1988 May;62(5):1814-8 - PubMed
- J Virol. 1988 Jun;62(6):1917-24 - PubMed
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