Hepatocyte growth factor at S phase induces G2 delay through sustained ERK activation.
The effect of growth factors on the cell cycle progression, except G1/S transition, is poorly understood. Herein, we examined the effect of hepatocyte growth factor (HGF) treated at S phase on the cell cycle progression of HeLa cells. Interestingly, the treatment resulted in G2 delay, evidenced by flow cytometric and mitotic index analyses. The delay corresponded with the delay of degradation of cyclin A and cyclin B, and the delay of decrease of Cdk1/cyclin B and Cdk2/cyclin A kinase activities. As for the signaling responsible, sustained activation of ERK, but neither of p38MAPK nor of JNK, was observed after HGF treatment at S phase. Furthermore, U0126, an inhibitor of MEK1, and DN-MEK partially abrogated the G2 delay, indicating that activation of MEK-ERK pathway is involved. Taken together, HGF treatment of HeLa cells at S phase induces G2 delay partially through sustained activation of ERK signaling.
Park
Yun Yeon
YY
Department of Biochemistry, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
Nam
Hyun-Ja
HJ
Lee
Jae-Ho
JH
D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D008940:Mitotic Index; D009570:Nitriles / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D017228:Hepatocyte Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases