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	2002 Fellow			Carla Vanina Rothlin, Ph.D. Lab. of: Greg Erwin Lemke, Ph.D. Molecular Neurobiology Laboratory Salk Institute for Biological Studies 10010 N. Torrey Pines Road La Jolla, CA 92186 Tel: (858) 453-4100 x1314 Fax: (858) 455-6138 Email: rothlin@salk.edu

Country: ARGENTINA

Field: Neurobiology

Research Interest: Recent single mutant and compound mutant genetic studies have demonstrated that the three receptor tyrosine kinases of the Tyro 3 family - Tyro 3, Axl, and Mer - play essential roles in cellular homeostasis and survival in the mature nervous, immune, and reproductive systems (Lu et al., Nature 398, 723-728, 1999; Lu and Lemke, Science 293, 306-311, 2001). These results notwithstanding, many of the basic features of signal transduction through the three receptors remain to be elucidated. These include: the extent to which individual receptors (which are typically co-expressed) may heterodimerize, and the consequences of such heterodimerization for signaling; the degree to which the anticoagulant Protein S is, in addition to the related protein Gas6, a biologically relevant ligand for these receptors (see Godowski et al., Cell 82, 355-358, 1995); the potential synergistic activity of these ligands and sex steroids such as testosterone (Lu et al., Nature 398, 723-728, 1999); and the downstream signaling proteins that bind to the cytoplasmic domains of the receptors subsequent to their activation and autophosphorylation (Lu and Lemke, Science 293, 306-311, 2001). We will employ a series of cell-based receptor binding and activation assays using purified recombinant ligands and cultured cell lines expressing the three receptors singly and in all combinations, together with existing mutants in the Gas6, Tyro 3, Axl, and Mer genes, to address each of these outstanding questions.