Tissue-specific alternative splicing generates two isoforms of the trkA receptor

The TrkA receptor functions as a signal transducing receptor for nerve growth factor. In this report, we show that alternative splicing results in the production of two distinct TrkA isoforms in both rats and humans. These isoforms differ by virtue of a 6-amino acid insertion in their extracellular domain, the placement of which corresponds exactly with the breakpoint found in several human TrkA oncogenes. When tested in fibroblasts, the presence (trkAII) or absence (trkAI) of the 6-amino acid insert does not affect the receptor's ligand binding specificity or its ability to transduce functional signals in response to nerve growth factor. In rats and humans, trkAII is the only isoform expressed within neuronal tissues at appreciable levels whereas trkAI, the form of TrkA originally cloned, appears to be expressed mainly in non-neuronal tissues.