# Decoding the phosphorylation bar code in Arabidopsis G Biased Signaling

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $378,602

## Abstract

Hormones and neurotransmitters modulate a variety of physiological processes in cell growth and
behavior. Their cognate cell surface receptors, which have seven transmembrane domains, act by coupling
to G proteins, promoting the dissociation of GDP and the subsequent loading of GTP. Signaling abates
when GTP is hydrolyzed and GTPase activity is accelerated by Regulators of G Signaling proteins having
GTPase accelerating protein (GAP) activity. Recently, we discovered a naturally-occurring 7TM-RGS
protein in Arabidopsis (AtRGS1) that is a glucose or nucleotide-sugar receptor. It is the prototype of a
receptor-GAP. We also showed that the Arabidopsis Gα subunit (AtGPA1) has rapid nucleotide exchange
making nucleotide hydrolysis the rate limiting step. This property is in marked contrast to the slow
nucleotide exchange property of all tested Gα subunits where GDP release is the rate limiting step of the
G protein cycle. In contrast to animals, regulation of the G protein cycle is at the GTP hydrolysis step and
is modulated by AtRGS1. This level of modulation is controlled by reversible phosphorylation of AtRGS1
and AtGPA1 at a mostly undeciphered set of phosphorylated amino acids designated here as the collective
phospho-bar code. We do know that one phosphorylation pattern on AtRGS1 is necessary and sufficient
to initiate AtRGS1 endocytosis and another on AtGPA1 changes the rate of AtRGS1-dependent G cycling.
There are different clusters of complexes of the AtRGS1/G protein/kinase/phosphatase on the plasma
membrane and these different clusters are activated by different agonists. Furthermore, we hypothesize
that this initial clustering, the assortment of proteins in the cluster, and the subsequent trafficking of the
cluster components after activation is encrypted by the phospho-bar code. Using the power of a genetic
system will enable us to determine the physiological role of the bar code in a multicellular context. Both
hypothesis- and discovery-driven approaches will be taken to determine precisely what structure imparts
regulatory control. Our studies of the Arabidopsis G protein cycle have to date illustrated how the G-protein
cycle can be regulated by mechanisms distinct from the classical GEF. Consequently, a greater degree of
plasticity of the cycle is now appreciated and new entry points for regulation are revealed. Understanding
the structure underlying these new mechanisms will provide a new means to regulate other G protein
cycles. Understanding how AtRGS1 modulates the G protein cycle in a ligand-dependent manner opens
up new possibilities to regulate G protein cycles through drug therapies. The core elements of
heterotrimeric G protein coupled signaling are conserved in eukaryotes but the mechanism to regulate the
active state of the G protein is not. This variation, genetically encoded in organisms divergent by as much
as 1.6 billion years of evolution, represents the full range of plasticity of the G protein signaling system.
Unders...

## Key facts

- **NIH application ID:** 10141241
- **Project number:** 5R01GM065989-14
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** ALAN M. JONES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,602
- **Award type:** 5
- **Project period:** 2002-09-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141241

## Citation

> US National Institutes of Health, RePORTER application 10141241, Decoding the phosphorylation bar code in Arabidopsis G Biased Signaling (5R01GM065989-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10141241. Licensed CC0.

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