Dr. William Gray

Reversible Ser/Thr phosphorylation of proteins is a major regulatory mechanism of numerous cellular functions. Type 2C protein phosphatases (PP2Cs) represent a major class of Ser/Thr phosphatases, and defects in several human PP2Cs have been implicated in cancer, diabetes, heart disease, neural disorders, and stress signaling. However, little is known about the mechanisms by which PP2C activity is regulated.

The plant hormone auxin regulates virtually every aspect of plant growth and development. Small Auxin Up-RNA (SAUR) genes represent the largest class of auxin-induced genes. The SAUR19-24 subset of highly related SAUR proteins specifically interact with and inhibit the enzymatic activity of PP2C.D family phosphatases to promote cell expansion. In part, this involves SAUR proteins preventing PP2C.D-mediated dephosphorylation of a key regulatory site of plasma membrane H+-ATPases. The long-term goal of this project is to thoroughly understand the molecular mechanisms underlying auxin-mediated control of plant growth and development. More specifically, this work will characterize and illuminate the mechanism by which SAUR proteins regulate PP2C.D phosphatases to control auxin-mediated cell expansion and other aspects of growth and development.

These studies include genetic, molecular, biochemical, and structural approaches to elucidate the regulatory mechanisms by which SAURs control PP2C activity in the model plant Arabidopsis thaliana. This plant provides a powerful genetic system for investigating conserved regulatory processes within multicellular eukaryotes. PP2C.D functions will be revealed through genetic analyses and phosphoproteomic profiling experiments that will define PP2C.D regulated pathways and identify potential phosphoprotein substrates important for auxin-mediated growth. Secondly, the regulation of SAUR protein stability will be investigated to gain insight into the mechanism and developmental regulation plants employ to control the abundance and activity of this important family of PP2C inhibitors. Lastly, the structure of a SAUR-PP2C.D complex will be determined and tested in biochemical and genetic assays to illuminate the molecular mechanism of SAUR inhibition of PP2C.D activity at atomic resolution. The findings from this research will likely have direct parallels to the mechanisms human cells employ to regulate PP2C activity, as PP2C structure and function are highly conserved. Such detailed understanding of PP2C regulatory mechanisms will facilitate the development of novel therapeutic strategies to alter PP2C activity and combat disease. Further, as humans depend on plants for sources of food, fiber, medicine, and fuel, this work will elucidate plant growth control by the SAUR-PP2C.D regulatory module and potentially lead to novel strategies for manipulating plant growth to benefit human health.