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(Journal of Leukocyte Biology. 2002;71:329-338.)
© 2002 by Society for Leukocyte Biology

The synthetic chemoattractant peptide, Trp-Lys-Tyr-Met-Val-D-Met, enhances monocyte survival via PKC-dependent Akt activation

Yoe-Sik Bae, Youndong Kim, Jun Chul Park, Pann-Ghill Suh and Sung Ho Ryu

Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea

Correspondence: S. H. Ryu, Ph.D., Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31 Hyojadong, Pohang, 790-784, Korea. E-mail: sungho{at}postech.ac.kr

Previously, we showed that Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) stimulates superoxide generation and chemotactic migration in monocytes and neutrophils. In this study, we examined the effect of WKYMVm on monocyte survival. Serum starvation-induced monocyte death was attenuated in the presence of WKYMVm, which was abated when the cells were preincubated with LY294002, suggesting the involvement of phosphoinositide-3-kinase (PI 3-kinase) in the peptide-induced monocyte survival. WKYMVm stimulated ERK and Akt activity via PI 3-kinase activation in monocytes. We also investigated the signaling pathway of WKYMVm-induced ERK and Akt activation. The WKYMVm-induced ERK activation was PI 3-kinase-dependent but PKC-independent. However, Akt activation by WKYMVm was dependent not only on PI 3-kinase but also on the PKC pathway. When monocytes were incubated with WKYMVm, caspase-3 activity, which is important for cell death, was inhibited. Pretreatment of the cells with LY294002, GF109203X, and Go 6976 but not PD98059 blocked WKYMVm-induced monocyte survival and caspase-3 inhibition. In summary, the novel chemoattractant WKYMVm enhances monocyte survival via Akt-mediated pathways, and in this process, PKC and PI 3-kinase act upstream of Akt.

Key Words: PI 3-kinase • ERK • G-protein • caspase-3




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