Mechanisms of RGS protein regulation
G protein-coupled receptors (GPCRs) represent the largest family of receptors and are important drug targets with 40-60% of currently FDA approved drugs targeting the receptors themselves or downstream mechanisms. One important regulatory mechanism of G protein signaling is mediated through a family of GTPase accelerating proteins, Regulator of G protein Signaling (RGS) proteins. RGS proteins modulate GPCR signaling by binding to and accelerating GTP hydrolysis on active Gα subunits of heterotrimeric G proteins. This results in attenuation of duration and amplitude of GPCR signaling. The majority of the more than 20 RGS proteins identified to date also possess additional functions not related to their canonical effect on G proteins. In the past 20 years, RGS proteins have emerged as novel drug targets in numerous disease states, such as hypertension, cancer and Parkinson disease among others. RGS proteins are tightly regulated through transcriptional, epigenetic and posttranslational mechanisms, such as degradation through the ubiquitin-proteasomal pathway. Furthermore, expression of RGS proteins is often altered during pathogenesis, causing dysregulation in GPCR signaling, that can cause or worsen the disease. Thus, the work in our lab is focused on two central questions:
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The canonical action of RGS proteins. In its inactive state, Gα is bound to GDP. Upon receptor activation, GDP is exchanged for GTP, Gα dissociates from Gβγ and both can mediate signaling cascades. RGS proteins bind to GTP-bound Gα, accelerates GTP hydrolysis and effectively reducing amplitude and duration of GPCR signaling.
Adapted from: Sjögren B (2017) The evolution of RGS proteins as drug targets – 20 years in the making. IUPHAR Review 21. Br. J. Pharmacol. 174(6):427-437. |
News
July 2019
We are celebrating our first research grant from the NIH! The lab received a two-year R21 grant from the National Institute of Aging entitled: “Assay development and screening for small molecule RGS10 regulators to target neuroinflammation”.
December 2018
We welcome Jacob Verburgt as a new graduate student to the Lab! Jacob is a 1st year MCMP student.
August 2018
We welcome Qian Zhang as a new graduate student to the Lab! Qian comes to us from the Animal Sciences Program and has transferred to MCMP as a graduate student as of August 8. Welcome Qian!
February 2018
Dr. Sjogren has been elected Sectretary/Treasurer Elect for the Drug Discovery Division of the American Society for Pharmacology and Experimental Therapeutics (ASPET).
January 2018
Harrison McNabb and Brandon Crotchett, both 1st year MCMP students, joined the lab officially on Jan 1st. Also joining the lab is Renee Towers, an undergraduate student at Purdue. Welcome all!
December 2017
We can start calling it a lab now! We have a new lab technician, Stephanie Gonzalez, who joined us on December 6th. Stephanie is a Purdue alumni, who comes to us from Dow AgroSciences. Welcome Stephanie! We also have two 1st-year graduate students, Brandon Crotchett and Harrison McNabb, who will be joining the lab!
October 2017
The lab is up and running! The first experiments started October 31st and three rotation students have joined the lab for the next four weeks!
September 2017
The lab is starting to take form! A postdoc position is currently open!
August 2017
The Sjogren Lab is established in RHPH room 318! Stay tuned for more! The lab is currently looking for enthusiastic graduate students and postdocs (see "Open positions"). Email jsjogren@purdue.edu if interested!
We are celebrating our first research grant from the NIH! The lab received a two-year R21 grant from the National Institute of Aging entitled: “Assay development and screening for small molecule RGS10 regulators to target neuroinflammation”.
December 2018
We welcome Jacob Verburgt as a new graduate student to the Lab! Jacob is a 1st year MCMP student.
August 2018
We welcome Qian Zhang as a new graduate student to the Lab! Qian comes to us from the Animal Sciences Program and has transferred to MCMP as a graduate student as of August 8. Welcome Qian!
February 2018
Dr. Sjogren has been elected Sectretary/Treasurer Elect for the Drug Discovery Division of the American Society for Pharmacology and Experimental Therapeutics (ASPET).
January 2018
Harrison McNabb and Brandon Crotchett, both 1st year MCMP students, joined the lab officially on Jan 1st. Also joining the lab is Renee Towers, an undergraduate student at Purdue. Welcome all!
December 2017
We can start calling it a lab now! We have a new lab technician, Stephanie Gonzalez, who joined us on December 6th. Stephanie is a Purdue alumni, who comes to us from Dow AgroSciences. Welcome Stephanie! We also have two 1st-year graduate students, Brandon Crotchett and Harrison McNabb, who will be joining the lab!
October 2017
The lab is up and running! The first experiments started October 31st and three rotation students have joined the lab for the next four weeks!
September 2017
The lab is starting to take form! A postdoc position is currently open!
August 2017
The Sjogren Lab is established in RHPH room 318! Stay tuned for more! The lab is currently looking for enthusiastic graduate students and postdocs (see "Open positions"). Email jsjogren@purdue.edu if interested!
To develop a complete mind: study the science of art; study the art of science. Learn how to see. Realize that everything connects to everything else.
Leonardo da Vinci
