Disease relevance of sty

• To address the role of mammalian Sprouty homologues in angiogenesis, another form of branching morphogenesis, a recombinant adenovirus engineered to express murine Sprouty-4 selectively in endothelial cells, was injected into the sinus venosus of embryonic day 9.0 cultured mouse embryos [1].

High impact information on sty

• The Egfr triggers cell recruitment in the eye, and sprouty- eyes have excess photoreceptors, cone cells, and pigment cells [2].
• Our results indicate that Sprouty is a widespread inhibitor of Ras pathway signal transduction [2].
• In contrast to an earlier proposal that Sprouty is extracellular, we show by biochemical analysis that Sprouty is an intracellular protein, associated with the inner surface of the plasma membrane [2].
• sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways [3].
• These two proteins contain a cysteine-rich domain related to Sprouty (the SPR domain) at the carboxy terminus [4].

Biological context of sty

• Furthermore, overexpression of sprouty in wing veins and ovarian follicle cells, two other tissues where EGF signaling is required for patterning, results in phenotypes that resemble the loss-of-function phenotypes of Egf receptor [5].
• Four mammalian sprouty genes have been cloned, which appear to play an inhibitory role mainly in FGF- mediated lung and limb morphogenesis [6].
• Generation of homozygous sprouty mutant follicle-cell clones demonstrates an essential role for Sprouty in restricting EGFR activation throughout oogenesis [7].
• Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation [8].
• Mammalian Spry proteins have been shown to undergo tyrosine and serine phosphorylation in response to growth factor stimulation [9].

Anatomical context of sty

• In a differential display analysis to identify genes involved in patterning the mid/hindbrain region of the chick neural tube, we have identified a sprouty orthologue, sprouty2 [10].
• Recently, Spry has been identified as an inhibitor of fibroblast growth factor (FGF) signalling during Drosophila trachea development [11].
• This sry delta germ-line function was revealed by transgenic expression of a modified Sry delta protein, Sry DB56, carrying a two-finger swap [12].
• In cultured cells, inactivation of SHP-2 increases phosphorylation on the critical tyrosine of Sprouty 1 [13].
• Sry high mobility group (HMG) box (Sox) transcription factors are involved in the development of central nervous system (CNS) in all metazoans [14].

Associations of sty with chemical compounds

• Thus, Sprouty may regulate angiogenesis in normal and disease processes by modulating signaling by endothelial tyrosine kinases [1].

Physical interactions of sty

• Substrate-trapping forms of Corkscrew bind Sprouty in cultured Drosophila cells and the developing eye [13].

Regulatory relationships of sty

• Similarly, in wing imaginal discs, ectopic Sprouty abolishes activated MAP kinase induced by the EGF receptor pathway [7].
• At the stage when dorso-ventral polarity of the follicle cells is established, Sprouty limits the ventral expansion of the activating Gurken signal [7].
• The Drosophila Sprouty (SPRY) protein has been shown to inhibit the actions of epidermal growth factor and fibroblast growth factor [15].

Other interactions of sty

• Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila [5].
• Sprouty is a general inhibitor of receptor tyrosine kinase signaling [7].
• Sprouty was originally identified as an inhibitor of Drosophila FGF receptor signaling during tracheal development [7].
• Branchless/Breathless signaling includes a Sprouty-dependent negative feedback loop [16].
• Evidence for direct interaction between Sprouty and Cbl [17].

References