Phosphorylation of CREB, a cyclic AMP responsive element binding protein, contributes partially to lysophosphatidic acid-induced fibroblast cell proliferation.
Lysophospholipids regulate a wide array of biological processes including cell survival and proliferation. In our previous studies, we found that in addition to SRE, CRE is required for maximal c-fos promoter activation triggered by lysophosphatidic acid (LPA). c-fos is an early indicator of various cells into the cell cycle after mitogenic stimulation. However, role of CREB activation in LPA-stimulated proliferation has not been elucidated yet. Here, we investigate how LPA induces proliferation in Rat-2 fibroblast cell via CREB activation. We found that total cell number and BrdU-positive cells were increased by LPA. Moreover, levels of c-fos mRNA and cyclin D1 protein were increased via LPA-induced CREB phosphorylation. Furthermore, LPA-induced Rat-2 cell proliferation was decreased markedly by ERK inhibitor (U0126) and partially by MSK inhibitor (H89). Taken together, these results suggest that CREB activation could partially up-regulate accumulation of cyclin D1 protein level and proliferation of LPA-stimulated Rat-2 fibroblast cells.
Kwon
Yong-Jun
YJ
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, Gangwon-do 200-702, South Korea.
Sun
Yuanjie
Y
Kim
Nam-Ho
NH
Huh
Sung-Oh
SO
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
C508137:Creb1 protein, rat; C530106:Ccnd1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D008246:Lysophospholipids; D016760:Proto-Oncogene Proteins c-fos; D019938:Cyclin D1; D020929:Mitogen-Activated Protein Kinase Kinases; C032881:lysophosphatidic acid