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Time‐Resolved Signaling Pathways of Nerve Growth Factor Diverge Downstream of the p140trk Receptor Activation Between Chick Sympathetic and Dorsal Root Ganglion Sensory Neurons
Author(s) -
Klinz FranzJosef,
Heumann Rolf
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65031046.x
Subject(s) - trk receptor , autophosphorylation , nerve growth factor , tyrosine phosphorylation , tropomyosin receptor kinase a , phosphorylation , dorsal root ganglion , receptor tyrosine kinase , microbiology and biotechnology , biology , protein tyrosine phosphatase , tyrosine , medicine , endocrinology , tyrosine kinase , sensory neuron , neuroscience , signal transduction , protein kinase a , sensory system , receptor , biochemistry
We have recently shown that the small GTP binding protein p21 ras is essential for nerve growth factor (NGF)‐mediated survival of peripheral embryonic chick dorsal root ganglia (DRG) sensory but not sympathetic neurons. To investigate at which level of the signaling cascade the pathways diverge, we have studied the time‐resolved pattern of NGF‐stimulated tyrosine phosphorylation of proteins within 4 h after addition of the neurotrophin. In both chick sympathetic neurons [embryonic day (E) 12] and DRG sensory neurons (E9) NGF induces within 1 min the autophosphorylation of the receptor tyrosine kinase p140trk. However, the pattern of substrate protein tyrosine phosphorylation downstream of p140trk is distinctly different in both neuronal subtypes. In sympathetic neurons, we observe within 1 min the tyrosine phosphorylation of a new substrate protein, p105, reaching maximal levels at 3 min. Tyrosine phosphorylation of p105 remains elevated for up to 4 h. Subsequent to p105, NGF induces the tyrosine phosphorylation of p42, a protein belonging to the family of mitogen‐activated protein (MAP) kinases. This stimulation is transient, reaching maximal levels at 10 min and returning to very low levels already after 2 h. In DRG sensory neurons, tyrosine phosphorylation of p105 is weak and very short lived, disappearing already after treatment with NGF for 10 min. In contrast, activation of MAP kinase p42 in DRG sensory neurons is more stable than in sympathetic neurons. All NGF‐stimulated tyrosine phosphorylation events were inhibited by preincubation of neurons with the tropomyosin‐related kinase (trk) inhibitor K252a. We suggest the working hypothesis that persistent tyrosine phosphorylation of p105 may play a role in the p21ras‐independent NGF survival pathway of chick sympathetic neurons.