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The C2 domain of PKCdelta is a phosphotyrosine binding domain.

Benes CH, Wu N, Elia AE, Dharia T, Cantley LC, Soltoff SP.

Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

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 PKCdelta directly binds to phosphotyrosine peptides in a sequence-specific manner. We provide evidence that this domain mediates PKCdelta interaction with a Src binding glycoprotein, CDCP1. The crystal structure of the PKCdelta 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.

Publication Types:
PMID: 15851033 [PubMed - indexed for MEDLINE]