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Receptor tyrosine kinases mediate the extracellular signals and transmit them into the cytoplasm by activating intracellular proteins through tyrosine phosphorylation. Both Ephs and platelet-derived growth factor (PDGF) receptors (PDGFRs) have been implicated in neurogenesis, but the functional interaction between these two pathways is poorly understood. Here, we demonstrated that EphA4 directly interacts with PDGFRβ and mutually activates each other when expressed in HEK293T cells. H9-derived neural stem cells express Ephs and PDGFRs, and their proliferation is stimulated by ephrin-A1 and PDGF-BB with further augmentation by their combined application. As both EphA4 and PDGFRβ play important roles in preventing neurodegeneration and promoting neuroprotection, their interaction and transactivation might transduce the signal through the EphA4/PDGFRβ complex and augment the proliferation of neural stem cells.


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Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

Show Author's information Qingfa Chen1Takahiro Sawada2Kazushige Sakaguchi2( )Fabin Han1,3( )
Centre for Stem Cells and Regenerative Medicine, The Institute for Tissue Engineering & Regenerative Medicine, The Liaocheng People’s Hospital/Liaocheng University, Liaocheng, People’s Republic of China
Department of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan
Centre for Stem Cells and Regenerative Medicine, The Institute of Translational Medicine, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China

Abstract

Receptor tyrosine kinases mediate the extracellular signals and transmit them into the cytoplasm by activating intracellular proteins through tyrosine phosphorylation. Both Ephs and platelet-derived growth factor (PDGF) receptors (PDGFRs) have been implicated in neurogenesis, but the functional interaction between these two pathways is poorly understood. Here, we demonstrated that EphA4 directly interacts with PDGFRβ and mutually activates each other when expressed in HEK293T cells. H9-derived neural stem cells express Ephs and PDGFRs, and their proliferation is stimulated by ephrin-A1 and PDGF-BB with further augmentation by their combined application. As both EphA4 and PDGFRβ play important roles in preventing neurodegeneration and promoting neuroprotection, their interaction and transactivation might transduce the signal through the EphA4/PDGFRβ complex and augment the proliferation of neural stem cells.

Keywords: neural stem cell, proliferation, EphA4, PDGFRβ, transactivation

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Published: 06 July 2017
Issue date: December 2017

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© 2017 The Author(s).

Acknowledgements

All the participants in the study are appreciated. The authors are grateful to Dr Paul Lu from the University of California at San Diego for his help in preparing this manuscript and Dr Carl-Henrik Heldin from Ludwig Institute for Cancer Research for using their pcDNA3.1/PDGFRβ and pcDNA3.1/PDGFRβ(KD) plasmids. The work was supported by National Scientific Foundation of China (NSFC 81571241, to FH), a Research Grant on Priority Areas from the Wakayama Medical University (to KS and TS), and a Research Initiative Grant for Doctor from Liaocheng People’s Hospital (to QC).

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