Cell
Volume 121, Issue 2, 22 April 2005, Pages 271-280
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Article
The C2 Domain of PKCδ Is a Phosphotyrosine Binding Domain

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Summary

In eukaryotic cells, the SH2 and PTB domains mediate protein-protein interactions by recognizing phosphotyrosine residues on target proteins. Here we make the unexpected finding that the C2 domain of PKCδ directly binds to phosphotyrosine peptides in a sequence-specific manner. We provide evidence that this domain mediates PKCδ interaction with a Src binding glycoprotein, CDCP1. The crystal structure of the PKCδ C2 domain in complex with an optimal phosphopeptide reveals a new mode of phosphotyrosine binding in which the phosphotyrosine moiety forms a ring-stacking interaction with a histidine residue of the C2 domain. This is also the first example of a protein Ser/Thr kinase containing a domain that binds phosphotyrosine.

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These authors contributed equally to this work.