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Molecular basis for arrestin-mediated signaling

Award Number: R01GM120569
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: 08/01/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Molecular basis for arrestin-mediated signaling - PROJECT SUMMARY Arrestin proteins are master regulators of G protein coupled receptor (GPCR) signaling, and act in two ways. First, arrestins terminate the coupling of G proteins to cognate receptor by physically blocking the G protein coupling site. Second, arrestins can support G protein independent signaling. The best studied arrestin-mediated signaling pathways include the activation of mitogen activated protein (MAP) kinases and Src family kinases. Arrestins also have complex functions beyond the modulation of GPCR signaling. An increasing body of evidence suggests that arrestins may interact with some receptor tyrosine kinases (RTKs) and may also link RTKs to GPCR during some types of transactivation. In our last grant cycle, we expanded what is known about the function of arrestin in signaling, developed working assays for following arrestin functions in cells, and we developed a range of biochemical tools that can help to decipher how arrestins might link signaling cascades. Preliminary data from these advances include an arrestin-dependent signal initiation complex for MAP kinase activation. We leverage these findings, tools, and assays with three aims that explore the influence of arrestins on linking signal cascades, in three aims. In Aim 1, we combine in vitro structural and biophysical techniques (array assays, X-ray crystallography, and binding measurements) with functional measurements in cells to investigate how arrestins interact with RTKs. In Aim 2, we combine in cell assays with mutagenesis and functional analysis to reveal the requirements for arrestin to link RTKs with GPCRs during transactivation. In Aim 3, we use structural approaches to investigate arrestin-effector interactions.


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: 2025 ( Subtotal = $331,456 )
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	000	5	4/30/2025	COMPETING CONTINUATION	$331,456
														Subtotal = $331,456

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	000	4	11/11/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $310,075 )
2019	2019	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	000	4	7/1/2019	NON-COMPETING CONTINUATION	$310,075
														Subtotal = $310,075

Issue Date FY: 2018 ( Subtotal = $345,075 )
2018	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	000	3	7/2/2018	NON-COMPETING CONTINUATION	$310,075
2018	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	001	3	9/21/2018	SUPPLEMENT FOR EXPANSION	$35,000
														Subtotal = $345,075

Issue Date FY: 2017 ( Subtotal = $310,075 )
2017	2017	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	000	2	6/10/2017	NON-COMPETING CONTINUATION	$310,075
														Subtotal = $310,075

Issue Date FY: 2016 ( Subtotal = $303,270 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Biomedical Research and Research Training	000	1	8/1/2016	NEW	$303,270
														Subtotal = $303,270

Grand Total All Awards = $1,599,951

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Molecular basis for arrestin-mediated signaling

Award Number: R01GM120569

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: 08/01/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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