Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins

• DOI: 10.1073/pnas.94.12.6238
• Publication Date: 2002-07-26T14:31:39Z
• Authors: M. Sanicola; C. Hession; D. Worley; P. Carmillo; C. Ehrenfels; L. Walus; S. Robinson; G. Jaworski; H. Wei; R. Tizard; A. Whitty; R. B. Pepinsky; R. L. Cate
• Keywords: Neurturin; Proto-Oncogene Proteins c-ret

Glial cell line-derived neurotrophic factor (GDNF)-dependent activation of the tyrosine kinase receptor RET is necessary for kidney and enteric neuron development, mutations in are associated with human diseases. Activation by GDNF has been shown to require an accessory component, GDNFR-α (RETL1). We report isolation characterization rat cDNAs a novel cell-surface protein, RETL2, that shares 49% identity RETL1. Both RETL1 RETL2 can mediate dependent phosphorylation RET, but they exhibit different patterns expression fetal adult tissues. The most striking differences observed were central peripheral nervous systems. In addition, mechanisms which two proteins facilitate quite distinct. vitro binding experiments soluble forms demonstrate while binds tightly form membrane-associated complex then interact only high affinity presence RET. This strong dependence was confirmed FACS analysis on expressing cells. Together recent discovery related neurturin, these data raise possibility have distinctive roles during development system adult. represent new candidate susceptibility genes and/or modifier loci RET-associated