360회 The role of cAMP response element-binding protein, CREB as a tran…

360회

연사 :  허 성 오, 한림대학교 의과대학 약리학교실

제목: The role of cAMP response element-binding protein, CREB as a transcriptional regulator of Lysophospholipid signaling in neural progenitor and fibroblast cells

Abstract

 Lysophosphatidic acid (LPA) is a growth factor-like phospholipid that elicits a variety of cellular responses in numerous cell types, including neurons, immune cells and fibroblasts. Here, we investigated the possibility that LPA activates the transcription factor cAMP response element-binding protein, CREB, in H19-7 hippocampal progenitor cells and in Rat-2 fibroblast cells. CREB is activated in many cells downstream of signaling events such as growth factor and neurotrophin stimulation. We found that LPA rapidly stimulates phosphorylation of CREB at Ser133 in a time- and dose-dependent manner, as revealed by immunoblot analysis with a phosphospecific antibody recognizing CREB on Ser133. LPA-induced phosphorylation of CREB was dependent on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK). Inhibition of ERK1/2 with PD98059 and of p38 MAPK with SB203580, efficiently blocked LPA-mediated phosphorylation of CREB. The LPA-induced the CREB phosphorylation was abolished by H89, inhibitor of protein kinase A and of mitogen- and stress-activated protein kinase-1 (MSK1). Together, these data suggest that LPA stimulates nuclear transcription factor CREB via mitogen-activated protein kinase signaling components, ERK1/2, p38 MAPK, and MSK1 in Rat-2 fibroblast cells.