The nucleotide sequence for the human nerve growth factor (NGF) receptor has been determined. The 3.8 kb receptor mRNA encodes a 427 amino acid protein containing a 28 amino acid signal peptide, an extracellular domain containing four 40 amino acid repeats with six cysteine residues at conserved positions followed by a serinelthreonine-rich region, a single transmembrane domain, and a 155 amino acid cytoplasmic domain. The sequence of the extracellular domain of the NGF receptor predicts a highly ordered structure containing a negatively charged region that may serve as the ligand-binding site. This domain is conserved through evolution. Transfection of a full-length cDNA in mouse fibroblasts results in stable expression of NGF receptors that are recognized by monoclonal antibodies to the human NGF receptor and that bind [1251] NGF. introduction

During development of the vertebrate nervous system, nerve growth factor (NGF) plays an essential role in the survival and maintenance of the sympathetic and sensory neurons (Levi-Montalcini and Angeletti, 1963, 1968). NGF promotes nerve fiber outgrowth from embryonic sensory and sympathetic ganglia in vivo and in vitro (Thoenen and Sarde, 1980). NGF was the first growth factor to be identified, and it remains the only neurotrophic factor that has been shown to be responsible for neuronal survival in vivo. NGF has a role in the development of cholinergic neurons of the basal forebrain (Gnahn et al., 1983). In addition to trophic effects, NGF also has chemotactic properties. Neurites grow in a local environment in which NGF is present and may be guided directionally by NGF (Letourneau, 1978; Gunderson and Barrett, 1979; Campenot, 1978).