Protein tyrosine kinase 7 has a conserved role in Wnt/β‐catenin canonical signalling

Puppo, Francesca; Thomé, Virginie; Lhoumeau, Anne Catherine; Cibois, Marie; Gangar, Akanksha; Lembo, Frédérique; Belotti, Edwige; Marchetto, Sylvie; Lécine, Patrick; Prébet, Thomas; Sebbagh, Michaël; Shin, Won Sik; Lee, Seung Taek; Kodjabachian, Laurent; Borg, Jean-Paul

doi:10.1038/embor.2010.185

Cited by 93 publications

(128 citation statements)

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“…Indeed, PTK7 is implicated in the canonical and noncanonical Wnt pathways (17,39), which are thought to be the guardians of the balance between HSC selfrenewal and HSC differentiation (32). We showed recently that PTK7 plays a role in the canonical pathway downstream of Wnt3a, suggesting that deficiency in PTK7 may mirror deficiency in Wnt3a (25). This would be consistent with results showing that Wnt3a deficiency leads to a reduction in the numbers of HSPCs in the FL but would not fit with the reduced reconstitution capacity observed in secondary transplantation assays of Wnt3a-deficient cells, which is not observed with Ptk7-deficient cells (40).…”

Section: Discussionmentioning

confidence: 99%

“…Such a function of PTK7 in the Wnt5a-mediated noncanonical pathway would fit with the PCP function of PTK7 and with the altered homing and migrating properties of Ptk7-deficient cells that likely depend on small Rho GTPase activation. Some studies showed that PTK7 regulates the balance between the Wnt canonical and noncanonical pathways by interacting with Dishevelled (26,46), ROR2 (42,47), b-catenin (25), and LRP6 (39). We unsuccessfully tried to identify downstream pathways that could be regulated by Ptk7 in HSCPs using a candidate gene/ protein approach.…”

Section: Discussionmentioning

confidence: 99%

“…PTK7 is a type I protein composed of seven Ig loops in its extracellular region, a transmembrane domain, and an intracellular region with a tyrosine kinase domain (17,18,22,23). Although PTK7 is catalytically inactive, the cytoplasmic domain containing the tyrosine kinase domain is mandatory for receptor function in vitro and in vivo (24)(25)(26)(27). Both extracellular and intracellular domains of PTK7 can be released from the plasma membrane following the sequential cleavage of the receptor by membrane type 1-matrix metalloproteinase/ADAM-17 and g-secretase, interfering with its PCP and promigratory activities (24,28,29).…”

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confidence: 99%

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Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration

Lhoumeau

Arcangeli

Grandis

et al. 2016

The Journal of Immunology

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International audienceHematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. Atthe top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features arecontrolled through key microenvironmental cues and regulatory pathways, such as Wnt signaling.We showed previously that PTK7,a tyrosine kinase receptor involved in planar cell polarity, plays a role in epithelial Wnt signaling; however, its function in hematopoiesishas remained unexplored. In this article, we show that PTK7 is expressed by hematopoietic stem and progenitor cells, withthe highest level of protein expression found on HSCs. Taking advantage of a Ptk7-deficient mouse strain, we demonstrate that loss ofPtk7 leads to a diminished pool of HSCs but does not affect in vitro or in vivo hematopoietic cell differentiation. This is correlatedwith increased quiescence and reduced homing abilities of Ptk7-deficient hematopoietic stem and progenitor cells, unraveling noveland unexpected functions for planar cell polarity pathways in HSC fate

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration

Lhoumeau

Arcangeli

Grandis

et al. 2016

The Journal of Immunology

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“…The nature of its specific binding partners and the multifunctional role of PTK7 in cell migration are yet to be elucidated. It is likely that in different cell systems, PTK7 is involved in the interactions with Plexin1 (41), receptor for activated protein kinase C (RACK1) (40), vascular endothelial growth factor receptor 1 (FLT-1) (39), disheveled (dsh) (43), Van Gogh-like 2 (VANGL2) (17,30) and ␤-catenin (48).…”

Section: Discussionmentioning

confidence: 99%

Potential Relation of Aberrant Proteolysis of Human Protein Tyrosine Kinase 7 (PTK7) chuzhoi by Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) to Congenital Defects

Golubkov

Aleshin

Strongin

2011

Journal of Biological Chemistry

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Membrane PTK7 pseudo-kinase plays an essential role in planar cell polarity and the non-canonical Wnt pathway in vertebrates. Recently, a new N-ethyl-N-nitrosourea-induced mutant named chuzhoi (chz) was isolated in mice. chz embryos have severe birth defects, including a defective neural tube, defective heart and lung development, and a shortened anterior-posterior body axis. The chz mutation was mapped to the Ala-Asn-Pro tripeptide insertion into the junction region between the fifth and the sixth Ig-like domains of PTK7. Unexpectedly, chz reduced membrane localization of the PTK7 protein. We hypothesized and then proved that the chz mutation caused an insertion of an additional membrane type 1 matrix metalloproteinase cleavage site in PTK7 and that the resulting aberrant proteolysis of chz affected the migratory parameters of the cells. It is likely that aberrations in the membrane type 1 matrix metalloproteinase/PTK7 axis are detrimental to cell movements that shape the body plan and that chz represents a novel model system for increasing our understanding of the role of proteolysis in developmental pathologies, including congenital defects.About three of every 100 babies born in the United States have congenital abnormalities. Congenital abnormalities are ranked 34th of the top 50 causes of total death in the United States. Debilitating cardiovascular and nervous system defects jointly represent 40% of birth defects. The death toll of congenital abnormalities (0.58%) roughly equals that of stomach, skin, or oral cancers. Mechanistic research into birth defects is required to more efficiently contribute to prevention and correction of these disorders.The canonical, ␤-catenin-dependent and non-canonical, ␤-catenin-independent Wnt signaling pathways are conserved in eukaryotes and are critical for the diverse events in embryonic development and disease. The non-canonical Wnt/planar cell polarity (PCP) 2 signaling controls cell organization within the tissue plane (1, 2). The Wnt/PCP signaling affects the actin cytoskeleton via RhoA GTPase activation through dishevelled associated activator of morphogenesis 1 (DAAM1) and dishevelled activator of morphogenesis 2 (DAAM2). The first PCP signaling events occur at a gastrulation stage of embryogenesis. These events regulate the polarized directed cell movement to accomplish convergent extension for the anterior-posterior body axis elongation, neural tube closure, and craniofacial morphogenesis (3-6). Convergent extension failure results in a shortened anterior-posterior body axis and widened lateral axis (convergent extension phenotype), a defective neural system, and craniofacial abnormalities.Ubiquitously expressed PTK7 (also called colon carcinoma kinase-4 (CCK-4)) is a Wnt coreceptor and a regulator of PCP in vertebrates (7-13). Membrane PTK7 includes seven extracellular Ig domains, a transmembrane region, and a catalytically inert cytoplasmic tyrosine kinase (PTK) domain (8,9,11,14). PTK7 is evolutionary conserved in humans and mice and also chicken klingon (KLG...

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“…(15) Also, PTK7 interacts with b-catenin, enhancing b-catenin-dependent transcriptional events. (16) These studies suggest that PTK7 plays a role in the canonical Wnt pathway, the non-canonical Wnt pathway, and the PCP signaling pathway.…”

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confidence: 99%

Oncogenic role of protein tyrosine kinase 7 in esophageal squamous cell carcinoma

et al. 2013

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Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer that is particularly prevalent in East Asian countries. Our previous expression profile analysis showed that the gene encoding protein tyrosine kinase 7 (PTK7) is upregulated in ESCC tissues. Here, we aimed to validate PTK7 as a prognostic factor and a candidate target for molecular treatment of ESCC. Both RT-PCR and Western blot analysis of tissues from ESCC patients revealed that PTK7 was significantly upregulated in tumor tissue samples of ESCC. Immunohistochemical staining of PTK7 showed that increased expression of PTK7 was inversely correlated with overall survival (P = 0.021). In vitro knockdown of PTK7 inhibited proliferation, survival, wound healing, and invasion of ESCC cells. In addition, PTK7 knockdown decreased phosphorylation of Akt, Erk, and focal adhesion kinase (FAK), important determinants of cell proliferation, survival, and migration. Therefore, our findings suggest that PTK7 has potential as a prognostic marker for ESCC and might also be a candidate for targeted therapy in the treatment of ESCC. (Cancer Sci 2013; 104: 1120-1126 E sophageal cancer is one of the most devastating malignancies. Despite recent developments in its management, advanced esophageal cancer is associated with high rates of local recurrence and distant metastasis.(1,2) Although there has been improvement in clinical outcome through multidisciplinary treatment strategies, (3)(4)(5) such as total mediastinal lymph node dissection, (6) and new diagnostic modalities such as positron emission tomography, (7) these developments have not proven satisfactory in preventing the high recurrence rates. Currently, the prognosis is only promising if the tumor is detected early and resected completely.Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer in East Asian countries.(8) It has a unique profile of clinical and anatomical characteristics that is distinct from those of esophageal adenocarcinoma, which is more prevalent in North America, UK, and Australia.(8) To develop prognostic diagnosis and effective therapeutics for ESCC, the identification of biomarkers is of vital importance. In a gene expression profiling analysis to pursue biomarkers, we identified protein tyrosine kinase 7 (PTK7; also known as colon carcinoma kinase-4 or CCK-4), as a candidate biomarker for ESCC. (9) Protein tyrosine kinase 7 is a receptor tyrosine kinase-like molecule containing an extracellular domain with seven immunoglobulin-like loops, a transmembrane domain, and a defective tyrosine kinase domain that resembles a catalytic domain but lacks catalytic activity.(10-12) Mice expressing a truncated form of PTK7 protein die perinatally, revealing a defect in neural tube closure and stereociliary bundle orientation. These findings implicate PTK7 as a regulator of planar cell polarity (PCP).(13) It has been shown that PTK7 recruits RACK1, which affects Dsh recruitment by interaction with PKCd1. (14) Interaction between PTK7...

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Protein tyrosine kinase 7 has a conserved role in Wnt/β‐catenin canonical signalling

Cited by 93 publications

References 14 publications

Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration

Ptk7-Deficient Mice Have Decreased Hematopoietic Stem Cell Pools as a Result of Deregulated Proliferation and Migration

Potential Relation of Aberrant Proteolysis of Human Protein Tyrosine Kinase 7 (PTK7) chuzhoi by Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) to Congenital Defects

Oncogenic role of protein tyrosine kinase 7 in esophageal squamous cell carcinoma

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