Abstract
We recently demonstrated that 2,6,diamino-N-([I-(oxotridecyl)-2-piperidinyl]methyl)-hexanamide (NPC 15437) is a selective inhibitor of PKC interacting at the regulatory domain of the enzyme. To further investigate the interaction of NPC 15437 with PKC we expressed a series of cDNAs encoding mutant PKC molecules in COS7 cells. NPC 15437 had no effect on the protein kinase activity of mutants lacking the N-terminal region of the C1 domain. Further, NPC 15437 was a competitive inhibitor of the activation of PKCα by phorbol ester and attenuated the binding of phorbol ester to the enzyme in intact cells. The present study demonstrates that mutant enzyme constructs can be used to localize the site of interaction of NPC 15437 with PKC to residues 12-42, which encodes the pseudosubstrate binding domain and part of the first cysteine-rich repeat sequence.
Original language | English (US) |
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Pages (from-to) | 120-123 |
Number of pages | 4 |
Journal | FEBS Letters |
Volume | 285 |
Issue number | 1 |
DOIs | |
State | Published - Jul 8 1991 |
Externally published | Yes |
Keywords
- Inhibitor
- NPC 15437
- Phorbol ester
- Protein kinase C
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology