Signaling pathways are complex and function to transmit signals from the extracellular environment into the cell. Analysis of results obtained from a high throughput siRNA screen led to the identification of Membrane protein palmitoylated 3 (MPP3) and Leukocyte Tyrosine Kinase (LTK) as novel negative regulators of the Wnt pathway. MPP3 is a MAGUK family protein and domain mapping studies indicated that the Guk domain plays a role in the negative regulation of the pathway. LTK, a receptor tyrosine kinase, has several transcript variants one of which lacks the entire kinase domain (LTK∆KD). While LTK∆KD interacted with the Wnt receptor Frizzled7, the full length LTK did not, suggesting distinct modes of pathway regulation. Analysis of neuronal cells, NIE115 and Neuro2a, demonstrated LTK is expressed and that cells are Wnt3a responsive, thereby providing a neuronal model system appropriate for further studies on the mechanism and biological role of LTK as a negative regulator of the Wnt pathway

Signaling pathways are complex and function to transmit signals from the extracellular environment into the cell. Analysis of results obtained from a high throughput siRNA screen led to the identification of Membrane protein palmitoylated 3 (MPP3) and Leukocyte Tyrosine Kinase (LTK) as novel negative regulators of the Wnt pathway. MPP3 is a MAGUK family protein and domain mapping studies indicated that the Guk domain plays a role in the negative regulation of the pathway. LTK, a receptor tyrosine kinase, has several transcript variants one of which lacks the entire kinase domain (LTK∆KD). While LTK∆KD interacted with the Wnt receptor Frizzled7, the full length LTK did not, suggesting distinct modes of pathway regulation. Analysis of neuronal cells, NIE115 and Neuro2a, demonstrated LTK is expressed and that cells are Wnt3a responsive, thereby providing a neuronal model system appropriate for further studies on the mechanism and biological role of LTK as a negative regulator of the Wnt pathway