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The Journal of Neuroscience, January 1, 2001, 21(1):176-185

An Evolutionarily Conserved Transmembrane Protein That Is a Novel Downstream Target of Neurotrophin and Ephrin Receptors

Haeyoung Kong¹, Jim Boulter², Janet L. Weber³, Cary Lai³, and Moses V. Chao¹

¹ Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York, ² Department of Psychiatry and Behavioral Sciences, University of California, Los Angeles, California, and ³ Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California

Appropriate development of nervous system connectivity involves a variety of processes, including neuronal life-and-death decisions, differentiation, axon guidance and migration, and synaptogenesis. Although these activities likely require specialized signaling events, few substrates unique to these neurotrophic functions have been identified. Here we describe the cloning of ankyrin repeat-rich membrane spanning (ARMS), which encodes a novel downstream target of neurotrophin and ephrin receptor tyrosine kinases, Trk and Eph, respectively. The amino acid sequence of ARMS is highly conserved from nematode to human, suggesting an evolutionarily conserved role for this protein. The ARMS protein consists of 1715 amino acids containing four putative transmembrane domains, multiple ankyrin repeats, a sterile  motif domain, and a potential PDZ-binding motif. In the rat, ARMS is specifically expressed in the developing nervous system and in highly plastic areas of the adult brain, regions enriched in Trks and Eph receptors. ARMS can physically associate with TrkA and p75 neurotrophin receptors. Moreover, endogenous ARMS protein is tyrosine phosphorylated after neurotrophin treatment of pheochromocytoma 12 cells and primary hippocampal neurons or ephrin B treatment of NG108-15 cells, demonstrating that ARMS is a downstream target for both neurotrophin and ephrin receptors.

Key words: neurotrophin; Trk; p75; ephrin; Eph; tyrosine kinase; tyrosine phosphorylation; ankyrin

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Copyright © 2001 Society for Neuroscience  0270-6474/01/211176-10$05.00/0

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