Nerve growth factor supports the survival of sympathetic ganglion neurons and nociceptive sensory neurons in dorsal root ganglia derived from the neural crest and ascending cholinergic neurons of the basal forebrain. Mutations in the tyrosine kinase receptor A gene, described recently in patients with congenital insensitivity to pain with anhidrosis, correlate well with the defective development of the nociceptive neurons. Human tyrosine kinase receptor A is a receptor tyrosine kinase which is phosphorylated in response to nerve growth factor. The binding of the nerve growth factor to tyrosine kinase receptor A stimulates homodimer formation and activation of tyrosine kinase activity. Phosphorylated tyrosine residues in tyrosine kinase receptor A cytoplasmic domain serve as anchors for binding downstream signaling molecules.
