Nerve growth factor stimulates MAPK via the low affinity receptor p75LNTR

AbstractApart from its high affinity receptor TrkA, nerve growth factor (NGF) can also stimulate the low affinity receptor p75LNTR 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 p75LNTR but not TrkA. We found a fast and transient phosphorylation of p42- and p44-MAPK after stimulation with NGF or C2-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