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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2001 Sep;92(9):959–967. doi: 10.1111/j.1349-7006.2001.tb01187.x

PI3‐kinase p85α Is a Target Molecule of Proline‐rich Antimicrobial Peptide to Suppress Proliferation of ras‐Transformed Cells

Koji Tanaka 1,†, Yoshinori Fujimoto 1,✉, Masako Suzuki 1, Yasuaki Suzuki 1, Takaaki Ohtake 1, Hiroyuki Saito 1, Yutaka Kohgo 1
PMCID: PMC5926840  PMID: 11572764

Abstract

PR‐39, which is an endogenous antimicrobial peptide, can bind to Src homology 3 domains of the NADPH complex protein p47phox and the signaling adapter protein p!30Cas. Recently, we have reported that PR‐39 gene transduction altered invasive activity and actin structure of human hepatocellular carcinoma cells, suggesting that this peptide affects cellular signaling due to its prolinerich motif. In order to clarify the mechanism of the PR‐39 functions, we transfected the PR‐39 gene into mouse NIH3T3 cells which had already been transformed with human activated k‐ras gene. The PR‐39 gene transfectant showed a reorganization of actin structure and suppression of cell proliferation both in vitro and in vivo. Decreases of MAP (mitogen‐activated protein) kinase activity, cyclin Dl expression and JNK activity were observed in the PR‐39 gene transfectant. Co‐immunoprecipitation analysis revealed that PR‐39 binds to PI3‐kinase p85α, which is a regulatory subunit of PI3‐kinase and one of the effectors by which ras induces cytoskeletal changes and stimulates mitogenesis. The PI3‐kinase activity of the PR‐39 gene transfectant was decreased compared with that of the ras transformant. These results suggest that PR‐39 alters actin structure and cell proliferation rate by binding to PI3‐kinase p85α and suppressing the PI3‐kinase activity.

Keywords: PR, 39, Antimicrobial peptide, P13 kinase, ras, Actin

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