The research proposal is a multifaceted project and cellular migration. Central elements in cell-associated proteolysis important to cell migration and tissue remodeling are urokinase (uPA) and its cell-surface receptor. We have previously demonstrated that the adhesiveness of monocytic cells is dependent upon uPA receptor occupancy and regulated by the uPA inhibitor plasminogen activator inhibitor type 1 (PAI-1) through uPA/PAI complex turnover. We have recently described a novel vitronectin receptor whose activity is coupled to uPA receptor occupancy. As a known function of vitronectin is to bind PAI-1, we hypothesize that uPA-induced vitronectin binding initiates cellular attachment and by potentiating uPA/PAI-1 complex formation regulates uPA-dependent proteolysis and initiates subsequent cell detachment. To test this hypothesis we will characterize the vitronectin receptor and determine the importance of uPA-induced vitronectin binding on pericellular proteolysis and cellular migration.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003169-05
Application #
2734932
Study Section
Special Emphasis Panel (ZHL1-CCT-M (M1))
Project Start
1994-07-01
Project End
1999-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Robinson, W; Waltz, D A (2000) FEV(1) as a guide to lung transplant referral in young patients with cystic fibrosis. Pediatr Pulmonol 30:198-202
Waltz, D A; Fujita, R M; Yang, X et al. (2000) Nonproteolytic role for the urokinase receptor in cellular migration in vivo. Am J Respir Cell Mol Biol 22:316-22
Waltz, D A; Natkin, L R; Fujita, R M et al. (1997) Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin. J Clin Invest 100:58-67