Receptor tyrosine kinases (REKs) initiate signal transduction pathways in response to the binding of growth factors and extracellular matrix components, culminating in alterations in cell growth and differentiation. REK is a recently-identified REK in the axl family, the members of which (axl, tyro3, c-mer,c-eyk) are characterized by an extracellular domain with two Ig domains and two fibronectin III domains (FNIII) that may be involved in the hemophilic and/or heterophilic activation of REK's protein tyrosine kinase activity. REK's preferentially expressed in the developing vertebrate nervous system and its overexpression in NIH3T3 cells causes malignant cell transformation. The work proposed here will characterize the expression pattern and normal function of REK in the chick brain and retina. I will pursue three lines of study: 1) I will determine the spatiotemporal localization of REK in embryonic chick brain and retina. 2) I will assess the ability of Trek to be activated by homophilic interactions. Also, gas6 and protein S, heterophilic ligands for axel and tyro 3, will be evaluated as heterophilic ligands for REK and 3) the normal function of REK in the growth and differentiation of cultured chick neural retinal cells well be assessed through the use of oligonucleotides designed to abrogate endogenous REK expression. This work will contribute to our understanding of neural development by characterizing a recently-identified component of an intracellular signalling pathway potentially involved in the control of cell growth and differentiation and in the signaling of cell-cell contacts.
| Fiordalisi, J J; Maness, P F (1999) Rek, an Axl/Tyro3-related receptor-class tyrosine kinase, is expressed in Muller glia and differentiating neural subpopulations in the avian retina. Exp Eye Res 68:201-10 |
