The C2 domain of PKCdelta is a phosphotyrosine binding domain.
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.
Benes
Cyril H
CH
Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Wu
Ning
N
Elia
Andrew E H
AE
Dharia
Tejal
T
Cantley
Lewis C
LC
Soltoff
Stephen P
SP
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D007668:Kidney / Q000166:cytology; D008969:Molecular Sequence Data; D019151:Peptide Library; D019000:Phosphotyrosine / Q000378:metabolism*; D011493:Protein Kinase C / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta; D017434:Protein Structure, Tertiary; D051381:Rats; D012469:Salivary Glands / Q000166:cytology
D019151:Peptide Library; D019000:Phosphotyrosine; C497260:Prkcd protein, rat; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta