PI3-kinase p85 alpha is a target molecule of proline-rich antimicrobial peptide to suppress proliferation of ras-transformed cells

Citation
K. Tanaka et al., PI3-kinase p85 alpha is a target molecule of proline-rich antimicrobial peptide to suppress proliferation of ras-transformed cells, JPN J CANC, 92(9), 2001, pp. 959-967
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
JAPANESE JOURNAL OF CANCER RESEARCH
ISSN journal
0910-5050 → ACNP
Volume
92
Issue
9
Year of publication
2001
Pages
959 - 967
Database
ISI
SICI code
0910-5050(200109)92:9<959:PPAIAT>2.0.ZU;2-D
Abstract
PR-39, which is an endogenous antimicrobial peptide, can bind to Src homolo gy 3 domains of the NADPH complex protein p47(phox) and the signaling adapt er protein p130(Cas). Recently, we have reported that PR-39 gene transducti on altered invasive activity and actin structure of human hepatocellular ca rcinoma cells, suggesting that this peptide affects cellular signaling due to its proline-rich motif. In order to clarify the mechanism of the PR-39 f unctions, we transfected the PR-39 gene into mouse NIH3T3 cells which had a lready been transformed with human activated k-ras gene. The PR-39 gene tra nsfectant showed a reorganization of actin structure and suppression of cel l proliferation both in vitro and in vivo. Decreases of MAP (mitogen-activa ted protein) kinase activity, cyclin DI expression and JNK activity were ob served in the PR-39 gene transfectant. Co-immunoprecipitation analysis reve aled that PR-39 binds to PI3-kinase p85 alpha, which is a regulatory subuni t 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 ge ne transfectant was decreased compared with that of the ras transformant. T hese results suggest that PR-39 alters actin structure and cell proliferati on rate by binding to PI3-kinase p85 alpha and suppressing the PI3-kinase a ctivity.