2009 Fiscal Year Final Research Report

Role of Spred/Sprouty in angiogenesis and lymphangiogenesis

Research Project

Project/Area Number	20790241
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	General medical chemistry
Research Institution	National Institute of Health Sciences
Principal Investigator	KATO Reiko National Institute of Health Sciences, 療品部, 主任研究官 (00333469)
Project Period (FY)	2008 – 2009
Keywords	血管 / リンパ管 / Ras / ERK / シグナル / チロシンキナーゼ / プロテインキナーゼC
Research Abstract	Sprouty/Spred family proteins negatively regulate ERK signaling activated by growth factors and cytokines. We have analyzed gene knockout mice of this family and found that Sproutys negatively regulate angiogenesis, while Spreds regulate lymphangiogenesis. Sprouty4 inhibits vascular endothelial growth factor-A (VEGF-A) induced ERK activation, while Spred1/2 efficiently inhibit VEGF-C, which is essential for lymphangiogenesis. We have identified the difference between Sproutys and Spreds.in the action of VEGFs signal transduction. We also found that human SPRED1 is responsible for neurofibromatosis type I like disease.