STRUCTURE AND ORGANIZATION OF THE HUMAN TRKA GENE ENCODING A HIGH-AFFINITY RECEPTOR FOR NERVE GROWTH-FACTOR

Nerve growth factor (NGF) induces neurite outgrowth and promotes survi val of embryonic sensory and sympathetic neurons. TRKA, a receptor tyr osine kinase cloned from a human colon cancer was later found to be ex pressed in the nervous system and phosphorylated in response to NGF. S omatic rearrangement(s) of the TRKA gene (also designated NTRK1) are r esponsible for formation of some oncogenes, Genetic defects in TRKA ar e responsible for a human disorder, congenital insensitivity to pain w ith anhidrosis (CIPA). We report here isolation and characterization o f the TRKA 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 r ule. Approximately 1.2 kb of the 5'-flanking regions was sequenced, an d putative regulatory elements were identified. These results will be useful for studies on the developmental and biological regulation of t he TRKA gene and for further characterization of mutations in CIPA pat ients as well as elucidation of mechanisms responsible for rearrangeme nt(s) observed in human tumors.