PTK7 Extracellular Domain (human, recombinant)

Inactive tyrosine-protein kinase 7 (PTK7) is a transmembrane receptor involved in morphogenesis.¹ It is composed of a signal peptide, seven immunoglobulin-like (Ig-like) domains, a transmembrane domain, a juxtamembrane domain, and a catalytically inactive tyrosine kinase domain.² PTK7 is expressed in pancreas, kidney, liver, lung, and placenta, as well as brain, heart, and melanocytes, and localizes to cell-cell junctions.^3,4 It also undergoes alternative splicing to generate isoforms that exhibit tissue-specific distributions.² Soluble PTK7 is produced by proteolytic cleavage of the extracellular domain by matrix metalloproteinase-14 (MMP-14), also known as membrane type-1 MMP (MT1-MMP).⁴ PTK7 plays a role in planar cell polarity, gastrulation, neural tube closure, neural crest migration, cardiac morphogenesis, and epidermal wound repair and participates in canonical and non-canonical Wnt signaling.¹ Ectopic expression of PTK7 without the kinase domain induces migration of murine hematopoietic cells expressing the human protein and recombinant human soluble PTK7 inhibits VEGF-induced capillary tube formation in human umbilical vein endothelial cells (HUVECs).^5,6 A PTK7-targeting antibody-drug conjugate containing the DNA topoisomerase I inhibitor exatecan (Item No. 35452) induces tumor regression in a breast cancer mouse xenograft model.⁷ Overexpression of PTK7 is associated with poor prognosis in patients with acute myeloid leukemia (AML).⁵ Cayman’s PTK7 Extracellular Domain (human, recombinant) protein consists of 685 amino acids, has a calculated molecular weight of 76.1 kDa, and a predicted N-terminus of Ala31 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is 86.7 kDa due to glycosylation.

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1. Peradziryi, H., Tolwinski, N.S., and Borchers, A. The many roles of PTK7: A versatile regulator of cell-cell communication. Arch. Biochem. Biophys. 524(1), 71-76 (2012).

2. Jung, J.W., Ji, A.R., Lee, J., et al. Organization of the human PTK7 gene encoding a receptor protein tyrosine kinase-like molecule and alternative splicing of its mRNA. Biochim. Biophys. Acta 1579(2-3), 153-163 (2002).

3. Park, S.K., Lee, H.S., and Lee, S.T. Characterization of the human full-length PTK7 cDNA encoding a receptor protein tyrosine kinase-like molecule closely related to chick KLG. J. Biochem. 119(2), 235-239 (1996).

4. Golubkov, V.S., Chekanov, A.V., Cieplak, P., et al. The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: Implications in cancer and embryogenesis. The Journal of Biological Chemisty 285(46), 35740-35749 (2010).

5. Prebet, T., Lhoumeau, A.-C., Arnoulet, C., et al. The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome. 116(13), 2315-2323 (2010).

6. Shin, W.-S., Maeng, Y.-S., Jung, J.-W., et al. Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis. Biochem. Biophys. Res. Commun. 371(4), 793-798 (2008).

7. Kong, C., Pu, J., Zhao, Q., et al. MTX-13, a novel PTK7-directed antibody-drug conjugate with widened therapeutic index shows sustained tumor regressions for a broader spectrum of PTK7-positive tumors. Mol. Cancer Ther. 22(10), 1128-1143 (2023).