THE RAT TRKC LOCUS ENCODES MULTIPLE NEUROGENIC RECEPTORS THAT EXHIBITDIFFERENTIAL RESPONSE TO NEUROTROPHIN-3 IN PC12-CELLS

Members of the Trk tyrosine kinase family have recently been identifie d as functional receptors of the NGF family of neurotrophins. Here we show the rat trkC locus to be complex, encoding at least four distinct polypeptides. Three of the encoded polypeptides are full-length recep tor tyrosine kinases that differ by novel amino acid insertions in the kinase domain. A fourth protein is a truncated receptor that lacks th e catalytic domain. Tyrosine phosphorylation, cross-linking, and ligan d binding assays indicate that TrkC receptors interact with NT-3 and n ot with the related neurotrophins NGF, BDNF, xNT-4, or hNT-5. Furtherm ore, high and low affinity NT-3-binding sites are associated with the TrkC receptors. Stable and transient expression of TrkC receptors in P C12 cells indicates that the neurite outgrowth response elicited by NT -3 is dramatic in receptors lacking the novel kinase insert (gp150trkC ) but absent in receptors containing the 14 amino acid insert in the k inase domain (gp150trkC14). These data suggest that the trkC locus enc odes receptors that may be capable of mediating different biological r esponses within the cell. This could have important implications in un derstanding the role of neurotrophins in the development of the verteb rate nervous system.