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Published on: May 3, 2016
PTK7 proteolytic fragment proteins function during early Xenopus development
Hava Lichtig1, Yasmin Cohen1, Naama Bin-Nun1
1Department of Biochemistry, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, 31096, Israel.
Abstract:
Protein Tyrosine Kinase 7 (PTK7) is as a critical regulator of canonical and non-canonical Wnt-signaling during embryonic development and cancer cell formation. Disrupting PTK7 activity perturbs vertebrate nervous system development, and also promotes human cancer formation. Observations in different model systems suggest a complex cross-talk between PTK7 protein and Wnt signaling. During Xenopus laevis nervous system development, we previously showed that PTK7 protein positively regulates canonical Wnt signaling by maintaining optimal LRP6 protein levels, but PTK7 also acts in concert with LRP6 protein to repress non-canonical Wnt activity. PTK7 is a transmembrane protein, but studies in cancer cells showed that PTK7 undergoes "shedding" by metalloproteases to different proteolytic fragments. Some PTK7 proteolytic fragments are oncogenic, being localized to alternative cytoplasmic and nuclear cell compartments. In this study we examined the biological activity of two proteolytic carboxyl-terminal PTK7 proteolytic fragments, cPTK7 622-1070 and cPTK7 726-1070 during early Xenopus nervous system development. We found that these smaller PTK7 proteolytic fragments have similar activity to full-length PTK7 protein to promote canonical Wnt-signaling via regulation of LRP6 protein levels. In addition to cancer systems, this study shows in vivo proof that these smaller PTK7 proteolytic fragments can recapitulate full-length PTK7 protein activity in diverse systems, such as vertebrate nervous system development.
Insights
Smaller fragments of Protein Tyrosine Kinase 7 (PTK7) effectively regulate Wnt signaling and LRP6 protein levels. These findings demonstrate that PTK7 fragments can mimic full-length PTK7 activity in vertebrate development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cancer Biology
Background:
- Protein Tyrosine Kinase 7 (PTK7) is crucial for embryonic development and cancer.
- PTK7 regulates both canonical and non-canonical Wnt signaling pathways.
- PTK7 activity is linked to nervous system development and human cancer formation.
Purpose of the Study:
- To investigate the biological activity of carboxyl-terminal PTK7 proteolytic fragments (cPTK7 622-1070 and cPTK7 726-1070).
- To determine if these fragments can recapitulate the functions of full-length PTK7 during early Xenopus nervous system development.
Main Methods:
- Studied the effects of specific PTK7 fragments (cPTK7 622-1070, cPTK7 726-1070) in Xenopus laevis embryos.
- Assessed the impact of these fragments on canonical Wnt signaling and LRP6 protein levels.
- Compared the activity of PTK7 fragments to full-length PTK7 protein.
Main Results:
- The examined PTK7 proteolytic fragments (cPTK7 622-1070 and cPTK7 726-1070) demonstrated significant biological activity.
- These fragments promoted canonical Wnt signaling by regulating LRP6 protein levels, similar to full-length PTK7.
- In vivo evidence confirmed that smaller PTK7 fragments can replicate full-length PTK7 activity in vertebrate development.
Conclusions:
- Carboxyl-terminal PTK7 fragments retain the ability to modulate Wnt signaling and LRP6 levels.
- These findings highlight the functional relevance of PTK7 fragments in vertebrate nervous system development.
- PTK7 fragments may serve as functional mimics of the full-length protein in developmental contexts.
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