SPRED proteins and their roles in signal transduction, development, and malignancy
Abstract
The roles of SPRED proteins in signaling, development, and cancer are becoming increasingly recognized. SPRED proteins comprise an N-terminal EVH-1 domain, a central c-Kit-binding domain, and C-terminal SROUTY domain. They negatively regulate signaling from tyrosine kinases to the Ras–MAPK pathway. SPRED1 binds directly to both c-KIT and to the RasGAP, neurofibromin, whose function is completely dependent on this interaction. Loss-of-function mutations in SPRED1 occur in human cancers and cause the developmental disorder, Legius syndrome. Genetic ablation of SPRED genes in mice leads to behavioral problems, dwarfism, and multiple other phenotypes including increased risk of leukemia. In this review, we summarize and discuss biochemical, structural, and biological functions of these proteins including their roles in normal cell growth and differentiation and in human disease.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 01, 2020
- Source ID
- 10.1101/gad.341222.120
Entities
People
- Claire Lorenzo
- Frank McCormick
Organizations
- National Institutes of Health
- United States Department of Defense