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

Abstract

Qingfa Chen,1 Takahiro Sawada,2 Kazushige Sakaguchi,2 Fabin Han1,3 1Centre 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; 2Department of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan; 3Centre 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: EphA4, PDGFRβ, neural stem cell, transactivation, proliferation

Keywords

• EphA4
• PDGFRβ
• Neural stem cell
• Trans-activation
• Proliferation