ISOLATION AND EXPRESSION ANALYSIS OF TYRO3, A MURINE GROWTH-FACTOR RECEPTOR TYROSINE KINASE PREFERENTIALLY EXPRESSED IN ADULT BRAIN

Growth factors and their receptors function in the nervous system to i nduce proliferation and differentiation of neuronal precursor cells an d to support survival of mature neurons. We have isolated a murine gro wth factor receptor tyrosine kinase using an anti-phosphotyrosine anti body screening procedure and studied the pattern of expression. The de duced amino acid sequence of the kinase has all the characteristics of a growth factor receptor and consists of a putative extracellular dom ain, a transmembrane domain, and a tyrosine kinase domain. Sequence co mparison with known receptor tyrosine kinases indicated that the murin e kinase is a mouse homolog of tyro3, tyro3 belongs to the Axd/Ufo gro wth factor receptor family. In the putative extracellular domain, ther e are two Ig-like domains and two fibronectin type III repeats which a re conserved in other members of the Axl/Ufo family receptors. Norther n blot hybridization analysis showed that tyro3 is expressed at high l evels in the brain of adult mice, although considerable expression was also observed in the testis. In situ hybridization analysis revealed that high levels of tyro3 are expressed in the cerebral cortex, the la teral septum, the hippocampus, the olfactory bulb, and in the cerebell um. The highest levels of tyro3 expression in the brain are associated with neurons. The preferential expression of tyro3 in specific region s of the adult mouse brain suggests that tyro3 may function as a novel neurotrophic factor receptor.