TISSUE-SPECIFIC ALTERNATIVE SPLICING GENERATES 2 ISOFORMS OF THE TRKARECEPTOR

The trkA receptor functions as a signal transducing receptor for nerve growth factor. In this report, we show that alternative splicing resu lts in the production of two distinct trkA isoforms in both rats and h umans. 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 teste d in fibroblasts, the presence (trkAII) or absence (trkAI) of the 6-am ino acid insert does not affect the receptor's ligand binding specific ity or its ability to transduce functional signals in response to nerv e growth factor. In rats and humans, trkAII is the only isoform expres sed within neuronal tissues at appreciable levels whereas trkAI, the f orm of trkA originally cloned, appears to be expressed mainly in non-n euronal tissues.