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Journal of Cell Communication and Signaling

, Volume 13, Issue 1, pp 113–118 | Cite as

CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi

  • Kunimasa OhtaEmail author
  • Eriko Aoyama
  • Shah Adil Ishtiyaq Ahmad
  • Naofumi Ito
  • Mohammad Badrul Anam
  • Satoshi Kubota
  • Masaharu TakigawaEmail author
Research Article
  • 552 Downloads

Abstract

Extracellular molecules coordinate the multiple signaling pathways spatiotemporally to exchange information between cells during development. Understanding the regulation of these signal molecule-dependent pathways elucidates the mechanism of intercellular crosstalks. CCN2/CTGF is one of the CCN family members that binds BMP2, fibronectin, aggrecan, FGFR2 - regulating cartilage and bone formation, angiogenesis, wound repair etc. Tsukushi (TSK), which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family, binds nodal/Vg1/TGF-β1, BMP4/chordin, Delta, FGF8, Frizzled4, and is involved in the early body formation, bone growth, wound healing, retinal stem cell regulation etc. These two secreted molecules are expressed in similar tissues and involved in several biological events by functioning as extracellular signaling modulators. Here, we examine the molecular interaction between CCN2 and TSK biochemically. Co-precipitation assay and Surface Plasmon Resonance measurement showed their direct binding with the Kd value 15.3 nM. Further, the Solid-phase Binding Assay indicated that TSK binds to IGFBP and CT domains of CCN2. Our data suggest that CCN2 and TSK exert their function together in the body formation.

Keywords

CCN2/CTGF Tsukushi Soluble molecule SLRP Vertebrate development 

Notes

Acknowledgements

The authors thank Mitsue Kumamaru and Megumi Takiguchi. We also thank all members of our labs for their technical assistance and for valuable helps. This study was supported by the Kumamoto University International Research Core for Stem Cell-based Developmental Medicine and HIGOprogram and in part by grants from the programs Grants-in-Aid for Scientific Research (B) to MT (#JP15H05014) and for Challenging Exploratory Research to MT (#JP17K19757) from Japan Society for the Promotion of Sciences, Japan.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  1. 1.Department of Developmental Neurobiology, Graduate School of Life SciencesKumamoto UniversityKumamotoJapan
  2. 2.Program for Leading Graduate Schools “HIGO Program”Kumamoto UniversityKumamotoJapan
  3. 3.Global COE Cell Fate Regulation Research and Education UnitKumamoto UniversityKumamotoJapan
  4. 4.Japan Agency for Medical Research and Development (AMED)TokyoJapan
  5. 5.Advanced Research Center for Oral and Craniofacial SciencesOkayama University Dental School/Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayamaJapan
  6. 6.Department of Biotechnology and Genetic EngineeringMawlana Bhashani Science and Technology UniversityTangailBangladesh

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