Project Details
Description
PROJECT SUMMARY
Reversible serine/threonine phosphorylation of proteins plays an essential regulatory function in numerous
cellular processes. Type 2C protein phosphatases (PP2Cs) comprise a major class of Ser/Thr phosphatases
(PPases), and defects in several human PP2Cs have been implicated in cancer, diabetes, cardiovascular
disease, neural disorders, and stress signaling. However, major gaps exist in understanding how PP2C
enzyme activity is regulated and what specific proteins and processes are under PP2C control. In plants,
PP2C.D PPases inhibit organ growth by repressing cell expansion. In part, this is accomplished by
dephosphorylation of a key regulatory phosphosite of plasma membrane (PM) H+-ATPases. The growth
hormone auxin stimulates cell expansion by inducing expression of Small Auxin Up RNA (SAUR) genes, which
encode novel proteins that bind to PP2C.D PPases to inhibit enzymatic activity. 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, the work described in this proposal will identify regulators and
downstream effectors of SAUR-PP2C.D signaling hubs involved in auxin-mediated cell expansion and the
integration of volumetric changes with diverse cellular processes to yield a coordinated growth response.
Phosphoproteomic studies have identified >140 proteins exhibiting altered phosphorylation in response to
auxin. This dataset overlaps substantially with phosphoproteins affected by SAUR overexpression, implicating
SAUR-PP2C.D modules as major regulators of the auxin phosphorylome during cell expansion. Using the
powerful genetic system of the model plant Arabidopsis, the proposed studies will investigate the functional
roles of select phosphoprotein candidates in auxin-induced growth and their regulatory interactions with SAUR-
PP2C.D modules. Detailed analysis of auxin’s regulation of PM H+-ATPase activity will also be conducted.
Auxin both inhibits H+-ATPase dephosphorylation via SAUR repression of PP2C.D activity and stimulates
activation by promoting ATPase phosphorylation by TMK1 and additional kinases, including orthologs of WNK
and SPAK/OSR kinases implicated in mammalian cell size control. All of these kinases interact with one
another and PP2C.D PPases, and research will address how kinase and phosphatase activities are
coordinated and mutually regulated. This work will elucidate PP2C functions and regulatory mechanisms,
identify PP2C.D effectors that modulate cell expansion, and illuminate how auxin coordinates diverse cellular
processes to control cell size. Given the conservation of PP2C function across kingdoms and the universal
process of cell size control, project findings will have broad impact, including implications into human
development and disease. Further, as humans depend on plants for sources of food, fiber, and
pharmaceuticals, the proposed studies will elucidate plant growth control by SAUR-PP2C.D regulatory
modules and facilitate novel strategies for manipulating plant growth to benefit human health.
Status | Finished |
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Effective start/end date | 5/15/22 → 3/31/23 |
Funding
- National Institute of General Medical Sciences: $387,500.00
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