Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Enlightening insights into receptor complexity (#132)

Kevin Pfleger 1 2 3
  1. Harry Perkins Institute of Medical Research, Nedlands, WA, Australia
  2. Centre for Medical Research, The University of Western Australia, Crawley, WA, Australia
  3. Dimerix Bioscience Limited, Nedlands, WA, Australia

The primary focus of my research to date has been the study of G protein-coupled receptors (GPCRs) that are critical for endocrine signalling. Indeed GPCRs are so fundamentally important that Robert Lefkowitz and Brian Kobilka were awarded the Noble Prize in 2012 "for studies of G protein-coupled receptors".

My investigations of how these receptors function at the molecular and cellular level has spanned ligand-receptor interactions, elucidation of receptor-arrestin-ubiquitin complexes, evidence for receptor-receptor functional interactions and real-time monitoring of receptor trafficking. Receptors of particular interest to me over the years have included those binding the gonadotrophin-releasing hormone, orexins, vasopressin, angiotensin II and chemokines.

Our studies of heteromerisation between the ἀ1A-adrenoceptor and CXC chemokine receptor 2 have illustrated how complex formation can result in novel heteromer-specific functional outcomes, and this example may have relevance to prostate disorders such as benign prostatic hyperplasia and even cancer.

Recently, the emphasis of my work has been on receptor complexes relevant to kidney disorders, especially in terms of clinically-relevant mutations of the vasopressin receptor 2 resulting in nephrogenic diabetes insipidus (NDI) and nephrogenic syndrome of inappropriate antidiuresis (NSIAD), as well as investigation of functional interactions between angiotensin II receptor type 1 and CC chemokine receptor 2 with a proposed role in chronic kidney disease.