Identification of Gas6, a putative ligand for sky and Ax1 receptor tyrosine kinases, as a novel neurotrophic factor for hippocampal neurons

Sky (also known as Tyro3 and Rse) is a member of the Axl/Sky/Mer receptor tyrosine kinase family and has two immunoglobulin-like repeats and two fibronectin type III-like repeats in the extracellular domain. Gash is a ligand for all members of the Axl family, each of which (Axl, Sky, and c-Mer) has different affinities to Gash. Physiological functions of Sky and Gash in the nervous system are not well understood, despite their importance, which is suggested by Sky structural features and its predominant expression in the brain. We found in the RNase protection assays that gash and sky mRNAs are expressed in the adult rat hippocampus and are similarly regulated during development. Expression levels were low during embryonic stages but gradually increased during development and reached the highest level in adulthood. Sky, but not Axl, immunoreactivity was observed in the adult hippocampus. Recombinant rat Gash attenuated hippocampal neuronal cell death that was caused by serum starvation in vitro, indicating that Gash is a novel neurotrophic factor for hippocampal neurons. Gash showed regulated expression in the sciatic nerve after nerve transection. Therefore, Sky and Gash have neurotrophic roles in the nervous system. (C) 2002 Wiley-Liss, Inc.