Intermolecular interactions of Sprouty proteins and their implications in development and disease.

Receptor tyrosine kinase (RTK) signaling is spatially and temporally regulated by a number of positive and negative regulatory mechanisms. These regulatory mechanisms control the amplitude and duration of the signals initiated at the cell surface to have a normal or aberrant biological outcome in development and disease, respectively. In the past decade, the Sprouty (Spry) family of proteins has been identified as modulators of RTK signaling in normal development and disease. This review summarizes recent advances concerning the biological activities modulated by Spry family proteins, their interactions with signaling proteins, and their involvement in cardiovascular diseases and cancer. The diversity of mechanisms in the regulation of Spry expression and activity in cell systems emphasizes the crucial role of Spry proteins in development and growth across the animal kingdom.