Abstract
The G protein-coupled receptor (GPCR) kinases (GRKs) are a family of seven serine/threonine kinases that are recruited to and activated by almost all agonist-occupied GPCRs. Upon recruitment and activation, GRK2 inhibits G protein-dependent signaling downstream of GPCRs both directly, for example by sequestering activated G proteins, and indirectly, by promoting the recruitment of β-arrestins, which sterically hinder further G protein activation and drive receptor internalization. In addition to switching off G protein signaling, GRK2 also initiates a number of G protein-independent signaling pathways downstream of activated GPCRs by recruiting scaffolding proteins or by phosphorylating non-GPCR substrates. Furthermore, it has recently become clear that the GRKs regulate signaling downstream of receptors that belong to families other than the GPCRs, including the transforming growth factor β (TGFβ) receptor and the toll-like receptor TLR4. Here we focus on recent studies demonstrating an important role for GRK2 in regulating signaling in both positive and negative ways downstream of various receptor tyrosine kinases (RTKs), including platelet-derived growth factor (PDGF) receptors, epidermal growth factor (EGF) receptors and insulin-like growth factor 1 (IGF-1) receptors.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.