TY  - JOUR
A1  - Piiper, Albrecht
A1  - Đikić, Ivan
A1  - Lutz, Manfred Paul
A1  - Leser, Jürgen
A1  - Kronenberger, Bernd
A1  - Elez, Robert
A1  - Cramer, Henning
A1  - Müller-Esterl, Werner
A1  - Zeuzem, Stefan
T1  - Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells
T2  - Journal of biological chemistry
N2  - In PC12 cells, a well studied model for neuronal differentiation, an elevation in the intracellular cAMP level increases cell survival, stimulates neurite outgrowth, and causes activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). Here we show that an increase in the intracellular cAMP concentration induces tyrosine phosphorylation of two receptor tyrosine kinases, i.e. the epidermal growth factor (EGF) receptor and the high affinity receptor for nerve growth factor (NGF), also termed Trk(A). cAMP-induced tyrosine phosphorylation of the EGF receptor is rapid and correlates with ERK1/2 activation. It occurs also in Panc-1, but not in human mesangial cells. cAMP-induced tyrosine phosphorylation of the NGF receptor is slower and correlates with Akt activation. Inhibition of EGF receptor tyrosine phosphorylation, but not of the NGF receptor, reduces cAMP-induced neurite outgrowth. Expression of dominant-negative Akt does not abolish cAMP-induced survival in serum-free media, but increases cAMP-induced ERK1/2 activation and neurite outgrowth. Together, our results demonstrate that cAMP induces dual signaling in PC12 cells: transactivation of the EGF receptor triggering the ERK1/2 pathway and neurite outgrowth; and transactivation of the NGF receptor promoting Akt activation and thereby modulating ERK1/2 activation and neurite outgrowth.

Erratum in: Correction: Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells. Journal of biological chemistry 2020 Oct 23;295(43):14792. doi: 10.1074/jbc.AAC120.016177.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76034
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-760342
SN  - 0021-9258
VL  - 277.2002
IS  - 46
SP  - 43623
EP  - 43630
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -