Nerve growth factor stimulates MAPK via the low affinity receptor p75(LNTR).
Apart from its high affinity receptor TrkA, nerve growth factor (NGF) can also stimulate the low affinity receptor p75(LNTR) and induce a Trk-independent signaling cascade. We examined the possible involvement of mitogen-activated protein kinase (MAPK) in this signaling pathway in neuronal cultures of the cerebellum of P2-aged rats and PCNA cells; both cell types express p75(LNTR) but not TrkA. We found a fast and transient phosphorylation of p42- and p44-MAPK after stimulation with NGF or C(2)-ceramide which proved to be sensitive to inhibition of MAPK kinase and protein kinase A (PKA). As stimulation with NGF also activated p21Ras it can be concluded that at least part of the observed MAPK activation was effected via p21Ras and via PKA.
Susen
K
K
Molekulare Neurobiochemie, Fakultät Chemie, Ruhr-Universität Bochum, 44780, Bochum, Germany.
Heumann
R
R
Blöchl
A
A
D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000187:drug effects* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
D004791:Enzyme Inhibitors; C064769:N-acetylsphingosine; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D015689:Oncogene Protein p21(ras); D013110:Sphingosine