Alternative titles; symbols
HGNC Approved Gene Symbol: PTK7
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38): 6:43,076,314-43,161,715 (from NCBI)
PTK7 is a planar cell polarity (PCP) receptor that belongs to the immunoglobulin (Ig) superfamily. PTK7 is controlled by the noncanonical Wnt pathway (see 164975) and organizes polarization of many epithelial tissues and organs within the plane, driving cell migration and cell intercalation of nonepithelial cells (summary by Lhoumeau et al., 2016).
Protein-tyrosine kinases (PTKs) play important roles in regulating cell proliferation and differentiation during development. Lee et al. (1993) isolated a 220-bp fragment of PTK7 cDNA through a screen designed to identify tyrosine kinase mRNAs expressed in normal human melanocytes. Park et al. (1996) isolated a full-length PTK7 cDNA and found that it encodes a receptor protein-tyrosine kinase-like molecule closely related to a chick kinase-like gene whose function was unknown. Mossie et al. (1995) independently isolated the PTK7 gene from colon carcinoma and designated it colon carcinoma kinase-4.
Lee et al. (1993) mapped a fragment of PTK7 to chromosome 6 by Southern blot analysis using a panel of human-hamster somatic cell hybrids. Banga et al. (1997) sublocalized the PTK7 gene to 6p21.1-p12.2 by fluorescence in situ hybridization.
Lu et al. (2004) demonstrated that a mutation in the mouse Ptk7 gene, which encodes an evolutionarily conserved transmembrane protein with tyrosine kinase homology, disrupts neural tube closure and stereociliary bundle orientation, and shows genetic interactions with a mutation in the mouse Van Gogh homolog Vangl2 (600533). Lu et al. (2004) also showed that PTK7 is dynamically localized during hair cell polarization, and that the Xenopus homolog of PTK7 is required for neural convergent extension and neural tube closure. Lu et al. (2004) concluded that their results identified PTK7 as a novel regulator of PCP in vertebrates.
Grimes et al. (2016) demonstrated that ptk7 mutant zebrafish, a faithful developmental model of idiopathic scoliosis, exhibit defects in ependymal cell cilia development and cerebrospinal fluid (CSF) flow. Transgenic reintroduction of Ptk7 in motile ciliated lineages prevented scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes yielded idiopathic scoliosis phenotypes. Grimes et al. (2016) defined a finite developmental window for motile cilia in zebrafish spine morphogenesis. Notably, restoration of cilia motility after the onset of scoliosis blocked spinal curve progression. Grimes et al. (2016) concluded that their results indicated a critical role for cilia-driven CSF flow as an underlying biologic cause of idiopathic scoliosis.
Using flow cytometric analysis, Lhoumeau et al. (2016) showed that Ptk7 expression was inversely correlated with hemopoietic differentiation in adult murine hemopoietic stem cells (HSCs). They observed perinatal lethality in Ptk7 -/- mice due to profound developmental defects, consistent with previous findings. Ptk7 -/- embryos exhibited cranial neural tube closure defect, gastroschisis, and kidney and forelimb abnormalities. Ptk7 -/- mice had a quantitative defect in HSCs. Ptk7 -/- fetal liver cells were more quiescent than wildtype fetal liver cells. Loss of Ptk7 resulted in a diminished pool of HSCs, but it did not affect hemopoietic cell differentiation in vivo or in vitro, and Ptk7 -/- cells had reduced homing abilities. Lhoumeau et al. (2016) concluded that PTK7 does not affect HSC differentiation but is critical for proliferation and migration.
Banga, S. S., Ozer, H. L., Park, S.-K., Lee, S.-T. Assignment of PTK7 encoding a receptor protein tyrosine kinase-like molecule to human chromosome 6p21.1-p12.2 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 76: 43-44, 1997. [PubMed: 9154124] [Full Text: https://doi.org/10.1159/000134511]
Grimes, D. T., Boswell, C. W., Morante, N. F. C., Henkelman, R. M., Burdine, R. D., Ciruna, B. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science 352: 1341-1344, 2016. [PubMed: 27284198] [Full Text: https://doi.org/10.1126/science.aaf6419]
Lee, S.-T., Strunk, K. M., Spritz, R. A. A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. Oncogene 8: 3403-3410, 1993. [PubMed: 8247543]
Lhoumeau, A.-C., Arcangeli, M.-L., De Grandis, M., Giordano, M., Orsoni, J.-C., Lembo, F., Bardin, F., Marchetto, S., Aurrand-Lions, M., Borg, J.-P. Ptk7-deficient mice have decreased hematopoietic stem cell pools as a result of deregulated proliferation and migration. J. Immun. 196: 4367-4377, 2016. [PubMed: 27183644] [Full Text: https://doi.org/10.4049/jimmunol.1500680]
Lu, X., Borchers, A. G. M., Jolicoeur, C., Rayburn, H., Baker, J. C., Tessier-Lavigne, M. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 430: 93-98, 2004. [PubMed: 15229603] [Full Text: https://doi.org/10.1038/nature02677]
Mossie, K., Jallal, B., Alves, F., Sures, I., Plowman, G. D., Ullrich, A. Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. Oncogene 11: 2179-2184, 1995. [PubMed: 7478540]
Park, S.-K., Lee, H.-S., 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: 235-239, 1996. [PubMed: 8882711] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a021228]