Disease relevance of Spred2

• Gene disruption of Spred-2 causes dwarfism [1].
• Spred-2(-/-) mice showed reduced growth and body weight, they had a shorter tibia length, and showed narrower growth plates as compared with wild-type mice [1].
• Here we show that lack of functional Spred-2 protein in mice caused a dwarf phenotype, similar to achondroplasia, the most common form of human dwarfism [1].

High impact information on Spred2

• Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation [2].
• We detected promoter activity and protein expression of Spred-2 in chondrocytes, suggesting an important function of Spred-2 in chondrocytes and bone development [1].
• Our observations suggest a model in which loss of Spred-2 inhibits bone growth by inhibiting chondrocyte differentiation through up-regulation of the MAPK signaling pathway [1].
• Stimulation of chondrocytes with different FGF concentrations showed earlier and augmented ERK phosphorylation in Spred-2(-/-) chondrocytes in comparison to Spred-2(+/+) chondrocytes [1].
• Spred1 and Spred2 suppressed constitutively activated RhoA (V14RhoA)-induced stress fiber formation and serum response factor activation [3].

Biological context of Spred2

• Similarly, deletion of the C-terminal Sprouty domain of Spred-1 does not affect cell-cycle progression of G(0)-synchronized cells through to S-phase following growth factor stimulation, while the Sprouty domain is required for Spred-2 function [4].
• Here, we show a detailed in situ analysis of a mouse strain with a trapped Spred-2 gene, bringing a beta-galactosidase and neomycin fusion gene (beta-geo) under the control of the endogenous Spred-2 promoter [5].

Anatomical context of Spred2

• In humans, Spred-2 was found to be strongly expressed in glandular epithelia and, at the subcellular level, its immunoreactivity was associated with secretory vesicles [6].

Associations of Spred2 with chemical compounds

• Both Spred-1 and Spred-2 are membrane-associated substrates of receptor tyrosine kinases and they act as negative regulators of the Ras pathway upon growth factor stimulation [6].

References