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Cell Mol Life Sci. 2010 Apr;67(7):1105-18. doi: 10.1007/s00018-009-0236-7. Epub 2009 Dec 30.

Isoform specific phosphorylation of p53 by protein kinase CK1.

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1
Venetian Institute of Molecular Medicine (VIMM), Via G. Orus, 2, 35129, Padova, Italy.

Erratum in

  • Cell Mol Life Sci. 2011 Mar;68(5):919.

Abstract

The ability of three isoforms of protein kinase CK1 (alpha, gamma(1), and delta) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide reproducing its 1-28 sequence. Both substrates are readily phosphoylated by CK1delta and CK1alpha, but not by the gamma isoform. Affinity of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K (m) 0.82 muM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1 is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and on a remote docking site mapped to the K(221)RQK(224) loop according to modeling and mutational analysis.

PMID:
20041275
DOI:
10.1007/s00018-009-0236-7
[Indexed for MEDLINE]

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