Disease relevance of SPRED1

• SPRED1 gene-disease database  
• Moreover, Spred expression levels in HCC tissue were inversely correlated with the incidence of tumor invasion and metastasis [1].
• Melanocytes from a café-au-lait spot showed, in addition to the germline SPRED1 mutation, an acquired somatic mutation in the wild-type SPRED1 allele, indicating that complete SPRED1 inactivation is needed to generate a café-au-lait spot in this syndrome [2].

High impact information on SPRED1

• Instead, Spred inhibited the activation of MAP kinase by suppressing phosphorylation and activation of Raf [3].
• These mutants reverted the suppressive effect of both Sprouty2 and Sprouty4 but not that of RasGAP or SPRED (Sprouty-related EVH1 domain-containing protein), another Sprouty-related Ras suppressor [4].
• Spred-1 overexpression also reduced the secretion of matrix metalloproteinase-9 (MMP-9) and MMP-2, which play important roles in tumor invasion and metastasis [1].
• Forced expression of Spred-1 inhibited HCC cell proliferation in vitro and in vivo, which was associated with reduced ERK activation [1].
• In addition, Spred-1 inhibited growth factor-mediated HCC cell motility [1].

Biological context of SPRED1

• We also demonstrate that the inhibitory function of Spred proteins is restricted to the Ras/MAPK pathway, that tyrosine phosphorylation is not required for this function, and that the Sprouty domain mediates heterodimer formation of Spred proteins [5].
• Sproutys and Sprouty-related proteins, Spred-1 and -2, are known inhibitors of fibroblast growth factor (FGF) signaling, which plays key role in lung branching morphogenesis and the development of other tissues [6].

Anatomical context of SPRED1

• SPRED-1 is expressed in hematopoietic cells, including eosinophils, and negatively controls the eosinophil numbers and functions by modulating IL-5 signaling [7].
• Spred expression is especially strong in the regions of new bud formation both in the peripheral mesenchyme as well as in the epithelium [6].

Associations of SPRED1 with chemical compounds

• SPROUTY (SPRY) and SPRED family genes encode inhibitors for receptor tyrosine kinase signaling cascades, such as those of FGF receptor family members and EGF receptor family members [8].

Analytical, diagnostic and therapeutic context of SPRED1

• Expression of a dominant negative form of Spred and Spred-antibody microinjection revealed that endogenous Spred regulates differentiation in these types of cells [3].

References