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THE FNK KINASE AND VASCULAR CELL GROWTH CONTROL

Award Number: R01HL067051
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2001
PERIOD OF PERFORMANCE END DATE: 06/30/2005

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THE FNK KINASE AND VASCULAR CELL GROWTH CONTROL - DESCRIPTION (Applicant's abstract): The long-term goal of the research in our laboratory is to understand the molecular mechanisms that regulate growth factor-stimulated cell cycle progression. Most cells in adult, higher organisms are generally in a quiescent non-proliferative state, referred to as the GO phase of the cell cycle. If activated by an appropriate extracellular mitogen, these cells can exit from the resting state and reinitiate cell proliferation. In the context of vascular biology, the onset of endothelial cell (EC) proliferation is associated with the pathogenesis of numerous "angiogenic diseases" (e.g., cancer, diabetic retinopathy) while smooth muscle cell (SMC) accumulation occurs during the development of atherosclerosis, transplant-associated arteriosclerosis and restenosis after vessel wall injury. It is likely that fibroblast growth factor (FGF)- 1 and FGF-2 play an important role in vascular cell growth control. These factors act by binding and thereby activating specific transmembrane receptor tyrosine kinases. This triggers downstream intracellular events, including the stimulation of protein phosphorylation cascades and the transcriptional activation of specific genes. We have used a differential display approach to identify FGF-inducible genes in NIH 3T3 cells and vascular cells. One of these genes, named Fnk, is an immediate-early response gene encoding a member of the polo family of structurally-related serine/threonine kinases. We hypothesize that Fnk expression and enzymatic activity is critical for growth factor-stimulated cell cycle progression. The specific aims of this proposal are: 1) To determine whether the addition of FGF-2 to quiescent murine NIH 3T3 cells promotes changes in Fnk synthesis, phosphoamino acid content, enzymatic activity and subcellular localization, 2) To identify candidate Fnk regulatory proteins and substrates by screening for Fnkbinding proteins, 3) To determine whether Fnk overexpression or underexpression alters NIH 3T3 cell, human microvascular EC, or human aortic SMC proliferation in vitro, and 4) To determine the phenotypic consequences of Fnk deficiency in vivo. It is anticipated that these studies will provide important information on the biological functions of the Fnk protein and its potential role in vascular cell growth control in vivo.


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: 2004 ( Subtotal = $371,250 )
2004	2004	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	4	7/22/2004	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$371,250
														Subtotal = $371,250

Issue Date FY: 2003 ( Subtotal = $308,400 )
2003	2003	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	3		NON-COMPETING CONTINUATION	$308,400
														Subtotal = $308,400

Issue Date FY: 2002 ( Subtotal = $308,400 )
2002	2002	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	2	3/20/2002	NON-COMPETING CONTINUATION	$308,400
														Subtotal = $308,400

Issue Date FY: 2001 ( Subtotal = $308,400 )
2001	2001	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	1	4/16/2001	NEW	$308,400
														Subtotal = $308,400

Grand Total All Awards = $1,296,450

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THE FNK KINASE AND VASCULAR CELL GROWTH CONTROL

Award Number: R01HL067051

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2001

PERIOD OF PERFORMANCE END DATE: 06/30/2005

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