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Korean J Physiol Pharmacol 2020; 24(2): 129-135

Published online March 1, 2020 https://doi.org/10.4196/kjpp.2020.24.2.129

Copyright © The Korean Journal of Physiology & Pharmacology.

Connecting the dots between SHP2 and glutamate receptors

Hyun-Hee Ryu1,2,3, Sun Yong Kim1,2, and Yong-Seok Lee1,2,3,*

Departments of 1Physiology and 2Biomedical Sciences, 3Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea

Correspondence to:*Yong-Seok Lee
E-mail: yongseok7@snu.ac.kr

Received: November 27, 2019; Revised: January 6, 2020; Accepted: January 7, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


SHP2 is an unusual protein phosphatase that functions as an activator for several signaling pathways, including the RAS pathway, while most other phosphatases suppress their downstream signaling cascades. The physiological and pathophysiological roles of SHP2 have been extensively studied in the field of cancer research. Mutations in the PTPN11 gene which encodes SHP2 are also highly associated with developmental disorders, such as Noonan syndrome (NS), and cognitive deficits including learning disabilities are common among NS patients. However, the molecular and cellular mechanism by which SHP2 is involved in cognitive functions is not well understood. Recent studies using SHP2 mutant mice or pharmacological inhibitors have shown that SHP2 plays critical role in learning and memory and synaptic plasticity. Here, we review the recent studies demonstrating that SHP2 is involved in synaptic plasticity, and learning and memory, by the regulation of the expression and/or function of glutamate receptors. We suggest that each cell type may have distinct paths connecting the dots between SHP2 and glutamate receptors, and these paths may also change with aging.

Keywords: AMPA receptor, Learning and memory, NMDA receptor, Rasopathy, Synaptic plasticity