| Abstract: | The transcription factor sterol regulatory element binding protein (SREBP)-1c plays a pivotal role in lipid metabolism. In this report we identified the main phosphorylation sites of MAPK-families, i.e. p38 stress-activated MAPK (p38), ERK-MAPK (ERK) or c-JUN N-terminal protein kinases (JNK) in SREBP-1c. The major phosphorylation sites of p38, i.e. serine 39 and threonine 402, are identical to those we recently identified in the splice-variant SREBP-1a. In contrast, ERK and JNK phosphorylate SREBP-1c at two major sites, i.e. threonine 81 and serine 93, instead of one site in SREBP-1a. Functional analyses of the biological outcome in the human liver cell line HepG2 reveals SREBP-1c phosphorylation dependent alteration in lipid metabolism and secretion pattern of lipid transporting proteins, e.g. ApoE or ApoA1. These results suggest that phosphorylation of SREBP-1c by different MAPKs interferes with lipid metabolism and the secretory activity of liver cells. |
