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DORN1 defines a new family of receptor kinase purinoreceptors (P2K)

Award Number: R01GM121445
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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DORN1 defines a new family of receptor kinase purinoreceptors (P2K) - Abstract: Current data indicate that that purinergic signaling can potentially affect every cell in the human body. Indeed, one theory is that extracellular ATP (eATP) is the oldest, extracellular signal involved in cell-cell communication. The mechanisms of purinergic signaling are well-established in animals and, indeed, support a multibillion dollar pharmaceutical industry. In contrast, relatively little is known about purinergic signaling in plants. Plants do not possess canonical P2X an P2Y purinoreceptors. Indeed, our lab previously identified a new class of purinoreceptors in plants, exemplified by plasma membrane lectin-receptor-like-kinases, P2K1 and P2K2. Our research indicates that purinergic signaling in plants is as ubiquitous and impactful as that found in mammals and, indeed, many of the downstream effects are similar. The differences seen, comparing plants and animals, are due largely to the unique biochemistry of the P2K receptors. These are unique receptors in that they possess both kinase and nucleotide cyclase activity. Hence, the primary aim of this proposal is to explore further the function of these receptors and, specifically, the relative contribution of these two activities to cellular response to eATP. Specific aim 1 will address the hypothesis that ATP released from plant cells activates both P2K1 nucleotide cyclase and kinase activity, which subsequently mediate distinct downstream, cellular responses. Study 1 will utilize mutant studies of P2K1 to define the relative contribution of these two activities to downstream signaling responses. Study 2 will explore the relative importance of P2K1 cyclase and kinase activity relative to the activation of cyclic nucleotide gated calcium channels (CNGC). Study 3 will examine whether activation of the cytoplasmic kinase, BIK1, via P2K1 phosphorylation leads to CNGC Ca2+ channel activation. Specific aim 2 will address the hypothesis that, as is the case in animals, plants likely have multiple purinoreceptors that may act in specific tissues, during specific stages of development or in response to specific stresses. Preliminary data argue that additional purinoreceptors exist in plants. Hence, Study 4 will seek to identify additional plant purinoreceptors using a variety of approaches. Most notable is our finding that mutations that suppress the phenotypes of p2k1 mutants do so in the apparent absence of any known purinoreceptor, clearly indicating that other mechanisms must exist. Preliminary data suggest that purinoreceptors mediate the negative effects of stress on plant growth. Study 5 will explore how wounding stress is coupled to a reduction in growth by exploring the role of an atypical basic-helix-loop-helix protein, previously implicated in growth regulation, that is a direct target of P2K1 phosphorylation. The net result of our work is to provide the comparative data to add to our overall understanding of purinergic signaling in higher eukaryotes, illustrating differences and similarities, and ultimately laying the basis for opportunities to manipulate these pathways for therapeutic applications.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $328,650 )
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	8	7/15/2024	NON-COMPETING CONTINUATION	$328,650
														Subtotal = $328,650

Issue Date FY: 2023 ( Subtotal = $328,650 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	7	7/17/2023	NON-COMPETING CONTINUATION	$328,650
														Subtotal = $328,650

Issue Date FY: 2022 ( Subtotal = $328,650 )
2022	2022	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	001	6	7/18/2022	NON-COMPETING CONTINUATION	$328,650
2022	2020	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	4	4/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $328,650

Issue Date FY: 2021 ( Subtotal = $328,650 )
2021	2021	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	5	6/24/2021	COMPETING CONTINUATION	$328,650
														Subtotal = $328,650

Issue Date FY: 2020 ( Subtotal = $294,785 )
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	4	7/15/2020	NON-COMPETING CONTINUATION	$294,785
														Subtotal = $294,785

Issue Date FY: 2019 ( Subtotal = $294,890 )
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	3	7/9/2019	NON-COMPETING CONTINUATION	$294,890
														Subtotal = $294,890

Issue Date FY: 2018 ( Subtotal = $294,991 )
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	2	7/21/2018	NON-COMPETING CONTINUATION	$294,991
														Subtotal = $294,991

Issue Date FY: 2017 ( Subtotal = $295,089 )
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	1	7/25/2017	NEW	$295,089
														Subtotal = $295,089

Grand Total All Awards = $2,494,355

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DORN1 defines a new family of receptor kinase purinoreceptors (P2K)

Award Number: R01GM121445

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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