02 Aug Scientists Describe Codes That Instruct Cell Signaling

MedicalResearch.com Interview with:

Dr. Eric Xu

H. Eric Xu, Ph.D.
Professor, Center for Cancer and Cell Biology
Van Andel Research Institute 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: G protein–coupled receptors (GPCRs) comprise the largest family of cell surface signaling receptors and drug targets, with about 30 percent of drugs currently on the market interacting with these receptors. GPCR signaling is primarily mediated through two pathways: G proteins or arrestins, each of which drives distinct physiologic and therapeutic effects on GPCR ligands. Current GPCR drugs often activate or block both pathways, leading to therapeutic effects as well as unwanted side effects.

An ideal GPCR drug will have a therapeutic effect but block the side-effects by selectively modulating either the G protein or arrestin pathway. The switch between the G protein and arrestin pathways is determined by the phosphorylation of the GPCR, the underlying mechanism of which has been a long sought-after question in the field.

Our study uncovered and validated the phosphorylation pattern, which serves as the instructional code to switch on the arrestin pathway. Furthermore, the code appears to be universally applicable to the proteome of GPCRs and could serve as a guiding light for understanding other GPCR-arrestin interactions and arrestin-biased signaling.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Many of the processes that underlie life can be compared to a secret book of instructional codes. The most pronounced of these is the genetic code in our DNA that contains instructions for the protein machines that are the workhorses of biology. In this analogy, phosphorylation codes are the instructions for cell signaling that determine the outcome of GPCR functions, which can be modulated by drugs to alter physiological states and disease processes.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: In the future, we plan to investigate whether the phosphorylation codes that we discovered are generally applicable to other non-GPCR membrane proteins because these membrane proteins also use arrestin or arrestin-like proteins to mediate their downstream functions, such as endocytosis. In addition, phosphorylation codes may be used in drug discovery to monitor the activation of biased signaling.

MedicalResearch.com: Is there anything else you would like to add?

Response: The boundaries of science are unlimited; every discovery always brings on new questions. Besides the phosphorylation codes, we want to know how these codes are generated by enzymes called GPCR kinases.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors

Edward Zhou ,Eric Xu et al
DOI: http://dx.doi.org/10.1016/j.cell.2017.07.002
Cell July 27 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on August 4, 2017 by Marie Benz MD FAAD