Carboxyl-terminus of the amyloid protein precursor and ERbeta are required for estrogenic effect in activating mitogen-activated protein kinase.
Estrogen influences the processing of the amyloid beta precursor protein (APP) in the pathogenesis of Alzheimer's disease, and this effect is mediated by estrogen receptors (ERs) in activating mitogen-activated protein kinase (MAPK)-signaling pathway. To test whether the estrogenic effect on both carboxyl-terminal amino acid fragment (C-terminal) of APP (APP-C105)- and ERbeta-mediated MAPK activation in in vitro, two hybrid genes containing each human ERbeta and APP-C105 gene fused to the neuron-specific enolase (NSE) promoter were constructed and were transfected to the neuronal SK-N-MC cells. Western blot shows that the activation of JNK-signaling pathway, but not p38 and ERK, is dependent on ERbeta through estrogen treatment and APP-C105 is also mediated through estrogen in activating MAPK-signaling pathway. The results suggest that ERbeta and APP-C105 derived from APP are necessary for estrogenic effect in activating MAPK-signaling pathway.
Lim
Hwa J
HJ
Division of Laboratory Animal Resources, Korea Food and Drug Administration, National Institute of Toxicological Research, Seoul 122-704, Republic of Korea.
Lim
Chul J
CJ
Hwang
Dae Y
DY
Lee
Su H
SH
Min
Sae H
SH
Song
Youn S
YS
Seo
Su J
SJ
Park
Hye K
HK
Sheen
Yhun Y
YY
Cho
Jung S
JS
Kim
Yong K
YK
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D047629:Estrogen Receptor beta; D004958:Estradiol; D020928:Mitogen-Activated Protein Kinases