Selective inhibition of rat mesangial cell proliferation by a synthetic peptide derived from the sequence of the C2 region of PKCbeta.
RACK (receptor for activated C-kinase) is a protein that binds and translocates protein kinase C (PKC) to the appropriate cellular organelles. The binding of RACK has been mapped to C2 region of PKC. A number of peptides from the C2 region of PKCbeta have been shown to inhibit the translocation and activation of PKCbeta. This investigation was undertaken to study the role of PKCbeta in rat mesangial cell proliferation mediated by a number of mitogens. Exposure of rat mesangial cells to thrombin, endothelin, epidermal growth factor, and phorbol 12,13-dibutyrate resulted in increased [3H]thymidine incorporation. Pretreatment of mesangial cells with Ro 32-0432 (selective PKC inhibitor) inhibited the proliferation mediated by all the above mitogens, suggesting that these mitogens mediated proliferation through PKC. Experiments were performed to further evaluate the involvement of PKCbeta in this process by using the peptide derived from the C-2 region of PKCbeta as a tool. The data suggest that although the peptide (P) alone had no effect on basal- or mitogen-mediated proliferation, the peptide in the presence of a carrier peptide (PC) inhibited proliferation mediated by endothelin. In the same experiment, proliferation mediated by epidermal growth factor, thrombin and phorbol dibutyrate was unaffected, suggesting that in rat mesangial cells, endothelin mediated proliferation through the activation of PKCbeta.
Wu
H L
HL
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Albrightson
C
C
Nambi
P
P
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007527:Isoenzymes / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000737:chemistry*; D064546:Protein Kinase C beta; D051381:Rats; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000737:chemistry*; D013917:Thrombin / Q000494:pharmacology
C400975:AAVALLPAVLLALLAP; D007527:Isoenzymes; D009842:Oligopeptides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D013917:Thrombin