• PTK7 (CCK4) is a non-active receptor tyrosine kinase originally identified in colon carcinoma cells. PTK7 functions in cell adhesion, cell migration, cell polarity, proliferation, actin cytoskeleton reorganization, and apoptosis to regulate embryogenesis, epithelial tissue organization, neuronal tube closure, neuronal crest formation, and axon guidance.
• PTK7 acts as a co-receptor in both the non-canonical (also known as the Wnt/planar cell polarity signaling) and the canonical Wnt signaling pathways. In the non-canonical Wnt pathway, PTK7 activates downstream signaling by direct interaction with RACK1 and recruitment of DSH into the membrane localized receptor complex.
• PTK7 exerts an inhibitory effect on canonical Wnt pathway signal transduction through competition for frizzled receptor binding at the membrane surface. PTK7 gene expression is regulated by Cdx, while protein stability is regulated by membrane associated proteinase degradation.
• PTK7 is targeted for proteolytic degradation and extracellular domain shedding by the metalloproteinases MMP14 and Adam17, leading to enhanced cell proliferatiion, migration, and facilitated cancer cell invasion. PTK7 has been shown to regulate other signaling pathways by functioning as a co-receptor with membrane receptors, such as Plexin A1 and VEGFR1.

Gene targeting strategy for B-hPTK7 mice. The exons 2–14 of the mouse Ptk7 gene, which encode the extracellular domain, were replaced by human counterparts in B-hPTK7 mice. The genomic region of the mouse Ptk7 gene encoding the signal peptide, transmembrane domain, and cytoplasmic portion was retained.

Strain specific analysis of PTK7 mRNA expression in wild-type C57BL/6 mice and B-hPTK7 mice by RT-PCR. Lung RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hPTK7 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human PTK7 primers. Mouse Ptk7 mRNA was detectable only in wild-type C57BL/6 mice. Human PTK7 mRNA was detectable only in homozygous B-hPTK7 mice but not in wild-type mice.

Western blot analysis of PTK7 protein expression in homozygous B-hPTK7 mice. Various tissue lysates were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hPTK7 mice (H/H), and then analyzed by western blot with anti-PTK7 antibody. 40 μg total proteins were loaded for western blotting analysis. PTK7 was detected in brain, lung and spleen from wild-type C57BL/6 mice and homozygous B-hPTK7 mice. The anti-PTK7 antibody was cross-reactive between human and mouse.