ABSTRACT
Growth promoting activity (GPA) is a chick growth factor with low homology to mammalian ciliary neurotrophic factor (CNTF) (47% sequence identity with rat CNTF) but displays similar biological effects on neuronal development. We have isolated a chick cDNA coding for a GPA receptor (GPAR α), a GPI-anchored protein that is 70% identical to hCNTFR α. Functional analysis revealed that GPAR α mediates several biological effects of both GPA and CNTF. Soluble GPAR α supports GPA- and CNTF-dependent survival of human TF-1 cells. In sympathetic neurons, GPAR α mediates effects of both GPA and CNTF on the expression of vasoactive intestinal peptide (VIP) as shown by the inhibition of GPA- and CNTF-mediated VIP induction upon GPAR α antisense RNA expression. These results demonstrate that GPAR α is able to mediate effects of two neurokines that are only distantly related. GPAR α mRNA expression is largely restricted to the nervous system and was detected in all neurons that have been shown to respond to GPA or CNTF by increased survival or differentiation, i.e. ciliary, sympathetic, sensory dorsal root, motoneurons, retinal ganglion cells and amacrine cells. Interestingly, GPAR α mRNA was additionally found in neuronal populations and at developmental periods not known to be influenced by GPA or CNTF, suggesting novel functions for GPAR α and its ligands during neurogenesis and neuron differentiation.