Characterization of a novel molluskan tyrosine kinase receptor that inhibits neurite regeneration

Receptor tyrosine kinases play many important roles in neuronal signaling including regulating neurite outgrowth. We have identified a novel receptor tyrosine kinase, neurite outgrowth regulating kinase (nork) from Aplysia californica. A fragment of this kinase was also identified in another mollusk, Lymnaea. The kinase domain is equally homologous to the Ret (rearranged during transformation) and fibroblast growth factor receptor families, but the extracellular domain is entirely novel, suggesting that it binds a nonconserved ligand. Overexpression of neurite outgrowth regulating kinase, but not a kinase dead form, causes a reduction in neurite outgrowth of Aplysia sensory neurons. Thus, we have identified a novel receptor tyrosine kinase implicated in regulating neurite outgrowth.