An Exploration of the Scope of GPCR to RTK Transactivation in HT22 and SH-SY5Y cells

Abstract

Receptor tyrosine kinase (RTK) transactivation is a mechanism by which G proteincoupled receptor (GPCR) activity induces the activation of an RTK. As separate families of receptors, they were long thought to act independently. Transactivation demonstrates an interconnectedness between these families that complicates molecular signalling significantly. Currently, most research on transactivation focuses on specific GPCR-RTK pairs. This leaves broader questions about the nature of transactivation unanswered. It is not yet known whether transactivation is universal to all GPCRs and RTKs or limited only to certain receptors. Additionally, the physiological relevance of transactivation is also still unknown. 8 different GPCR agonists were used to transactivate PDGFRα to determine which GPCRs are capable of transactivation. To complement this, 3 GPCR agonists were used to transactivate a large number of RTKs simultaneously, to determine which RTKs are capable of being transactivated. These two experiments together provide a broad look at the receptors on both sides of transactivation. In addition, experiments were performed in both a mouse and human cell line, as well as both undifferentiated and differentiated cells. This provides information on whether transactivation acts similarly in different species, cell types, and stages of development. By beginning to answer these questions about the nature of transactivation, we can provide a better perspective on where future research can proceed.