Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic β-cells

Michael Yedovitzky, Daria Mochly-Rosen, John A. Johnson, Mary O. Gray, Dorit Ron, Eva Abramovitch, Erol Cerasi, Rafael Nesher

Research output: Contribution to journalArticlepeer-review

164 Scopus citations


The protein kinase C (PKC) family consists of 11 isoenzymes. Following activation, each isoenzyme translocates and binds to a specific receptor for activated C kinase (RACK) (Mochly-Rosen, D. (1995) Science 268, 247-251) that provides an anchoring site in close proximity to the isoenzyme's specific substrate. Pancreatic islet cells contain at least six PKC isoenzymes (Knutson, K. L., and Hoenig, M. (1994) Endocrinology 135, 881-886). Although PKC activation enhances insulin release, the specific function of each isoenzyme is unknown. Here we show that following stimulation with glucose, αPKC and εPKC translocate to the cell's periphery, while δPKC and ζPKC translocate to perinuclear sites. βC2-4, a peptide derived from the RACK1- binding site in the C2 domain of βPKC, inhibits translocation of αPKC and reduces insulin response to glucose. Likewise, εV1-2, an εPKC-derived peptide containing the site for its specific RACK, inhibits translocation of εPKC and reduces insulin response to glucose. Inhibition of islet-glucose metabolism with mannoheptulose blocks translocation of both αPKC and εPKC and diminishes insulin response to glucose while calcium-free buffer inhibits translocation of αPKC but not εPKC and lowers insulin response by 50%. These findings illustrate the unique ability of specific translocation inhibitors to elucidate the isoenzyme-specific functions of PKC in complex signal transduction pathways.

Original languageEnglish (US)
Pages (from-to)1417-1420
Number of pages4
JournalJournal of Biological Chemistry
Issue number3
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic β-cells'. Together they form a unique fingerprint.

Cite this