The synthetic chemoattractant peptide, Trp-Lys-Tyr-Met-Val-D-Met, enhances monocyte survival via PKC-dependent Akt activation.
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.
Bae
Yoe-Sik
YS
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
Kim
Youndong
Y
Park
Jun Chul
JC
Suh
Pann-Ghill
PG
Ryu
Sung Ho
SH
D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D018945:Monocyte Chemoattractant Proteins; D009842:Oligopeptides; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C113617:Trp-Lys-Tyr-Met-Val-Met; C494918:AKT1 protein, human