Roles of the third Ig‐like domain of Necl‐5/PVR and the fifth Ig‐like domain of the PDGF receptor in its signaling

Abstract

The immunoglobulin (Ig)-like cell adhesion molecule nectin-like molecule (Necl)-5/poliovirus receptor is up-regulated in many types of cancer cells and implicated in their abnormally enhanced cell proliferation and movement. We previously showed that Necl-5 cis-interacts with the platelet-derived growth factor (PDGF) receptor β through the extracellular region and enhances its signaling. Although this cis-interaction does not affect the PDGF-induced tyrosine phosphorylation of the receptor, the interaction of the cytoplasmic region of Necl-5 with sprouty2 and the regulation of its activity are required for the enhancement of the PDGF receptor β signaling by Necl-5. We investigated here the more detailed mechanism for this cis-interaction of Necl-5 with the PDGF receptor β. Necl-5 contains three Ig-like domains and the PDGF receptor β contains five Ig-like domains at their extracellular regions. We showed here that the third Ig-like domain of Necl-5 cis-interacted with the fifth Ig-like domain of the PDGF receptor β. The recombinant protein of the third Ig-like domain of Necl-5 inhibited the cis-interaction of full-length Necl-5 with the PDGF receptor β and the PDGF-induced activation of the ERK signaling pathway that was enhanced by Necl-5. These results revealed the novel roles of the third Ig-like domain of Necl-5 and the fifth Ig-like domain of the PDGF receptor β in its signaling.

Re-Expression of Poly/Oligo-Sialylated Adhesion Molecules on the Surface of Tumor Cells Disrupts Their Interaction with Immune-Effector Cells and Contributes to Pathophysiological Immune Escape

“…Interestingly, VEGFR-2 can also interact with VE-cadherin [138,139], and VEGFR-1 with NRP-1 [133,134,[140][141][142][143]. Furthermore, PDGFR can interact with integrins, or NCAM, CADM1 [130,142], CD44 [144], Necl-5 [145], and TSP-1 [127]. Moreover, TGF-β can interact with syndecan-2 [146,147], NRP-1/NRP-2, and NCAM [108].…”