SPECIFICITY OF NEUROTROPHIN-3 DETERMINED BY LOSS-OF-FUNCTION MUTAGENESIS

Neurotrophin-3 (NT-3) is a member of the family of neurotrophic factor s, which also includes nerve growth factor (NGF) and which have specif ic activities on different subsets of vertebrate neurons, The aim of t his study was to determine which residues in NT-3 direct its specifici ty to the cognate TrkC receptor, It was possible to replace 80% of the residues in NT-3 with NGF residues without loss of specific activity. Residues D72, Y85, R87, W101, S107, and A111, together with either th e residues F12, V18, V20, M37, V42, F54, and K57 or the variable regio ns IV and V, accounted for the specificity of NT-3. It is concluded th at NGF and NT-3 use overlapping as well as separated regions for deter mination of specificities for their cognate receptors TrkA and TrkC, r espectively. (C) 1997 Wiley-Liss, Inc.