TY - JOUR
T1 - Regulated secretion of amyloid precursor protein by TrkA receptor stimulation in rat pheochromocytoma-12 cells is mitogen activated protein kinase sensitive
AU - Roßner, Steffen
AU - Ueberham, Uwe
AU - Schliebs, Reinhard
AU - Perez-Polo, J. Regino
AU - Bigl, Volker
N1 - Funding Information:
The authors wish to thank Dr. L. Reichardt (University of California, San Francisco, CA) for the donation of the anti-rat TrkA antibody. This work was supported by Schering AG and Bundesministerium für Forschung und Technik, grant No. 0310666 to V.B. and NIA grant AG10514 to J.R.P.-P. S.R. was the recipient of a fellowship granted by the Deutsche Akademie der Naturforscher LEOPOLDINA.
PY - 1999/8/20
Y1 - 1999/8/20
N2 - We have shown recently in the pheochromocytoma PC-12 cell line, that the activation of the high-affinity receptor for nerve growth factor (NGF), tyrosine kinase receptor (TrkA), results in increased secretion of the amyloid precursor protein (APP) into the culture medium. In order to reveal through which TrkA-associated signaling pathway the secretory APP processing is mediated, signaling cascades activated by TrkA stimulation were selectively inhibited under conditions of selective TrkA stimulation via non- NGF mechanisms and APP secretion into the culture medium was followed by Western analysis. Our data demonstrate, that activation of mitogen activated protein (MAP) kinase alone is sufficient to promote APP secretion, whereas inhibition of MAP kinase will reduce APP secretion only when phospholipase Cγ or phosphatidylinositol 3-kinase are additionally inhibited. This suggests that pharmacological manipulations activating the MAP kinase pathway may result in increased secretory APP processing.
AB - We have shown recently in the pheochromocytoma PC-12 cell line, that the activation of the high-affinity receptor for nerve growth factor (NGF), tyrosine kinase receptor (TrkA), results in increased secretion of the amyloid precursor protein (APP) into the culture medium. In order to reveal through which TrkA-associated signaling pathway the secretory APP processing is mediated, signaling cascades activated by TrkA stimulation were selectively inhibited under conditions of selective TrkA stimulation via non- NGF mechanisms and APP secretion into the culture medium was followed by Western analysis. Our data demonstrate, that activation of mitogen activated protein (MAP) kinase alone is sufficient to promote APP secretion, whereas inhibition of MAP kinase will reduce APP secretion only when phospholipase Cγ or phosphatidylinositol 3-kinase are additionally inhibited. This suggests that pharmacological manipulations activating the MAP kinase pathway may result in increased secretory APP processing.
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Mitogen activated protein kinase
KW - Nerve growth factor
KW - Phosphatidylinositol 3-kinase
KW - Phospholipase Cg
KW - Tyrosine kinase receptor A
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U2 - 10.1016/S0304-3940(99)00530-3
DO - 10.1016/S0304-3940(99)00530-3
M3 - Article
C2 - 10477111
AN - SCOPUS:0033588068
SN - 0304-3940
VL - 271
SP - 97
EP - 100
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -