Structure and organization of the humanTRKA gene encoding a high affinity receptor for nerve growth factor

Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. TRKA, a receptor tyrosine kinase cloned from a human colon cancer was later found to be expressed in the nervous system and phosphorylated in response to NGF. Somatic rearrangement(s) of theTRKA gene (also designatedNTRK1) are responsible for formation of some oncogenes. Genetic defects in TRKA are responsible for a human disorder, congenital insensitivity to pain with anhidrosis (CIPA). We report here isolation and characterization of theTRKA gene which spans at least 23 kb and is split into 17 exons. Exon sizes range from 18 to 394 bp and intron sizes range from 170 bp to at least 3.3 kb. Sizes and boundaries of the exons were determined, and all the splice donor and acceptor sites conformed to the GT/AG rule. Approximately 1.2 kb of the 5′-flanking regions was sequenced, and putative regulatory elements were identified. These results will be useful for studies on the developmental and biological regulation of theTRKA gene and for further characterization of mutations in CIPA patients as well as elucidation of mechanisms responsible for rearrangement(s) observed in human tumors.