화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.400, No.3, 299-304, 2010
Secreted Frizzled-related protein-2 (sFRP2) augments canonical Wnt3a-induced signaling
Secreted Frizzled-related proteins (sFRP) are involved in embryonic development as well as pathological conditions including bone and myocardial disorders and cancer Because of their sequence homology with the Writ-binding domain of Frizzled, they have generally been considered antagonists of canonical Wnt signaling However, additional activities of various sFRPs including both synergism and mimicry of Wilt signaling as well as functions other than modulation of Writ signaling have been reported Using human embryonic kidney cells (HEK293A), we found that sFRP2 enhanced Wnt3a-dependent phosphorylation of LRP6 as well as both cytosolic beta-catenin levels and its nuclear translocation. While addition of recombinant sFRP2 had no activity by itself, Top/Fop luciferase reporter assays showed a dose-dependent increase of Wnt3a-mediated transcriptional activity sFRP2 enhancement of Wnt3a signaling was abolished by treatment with the Writ antagonist, Dickkopf-1 (DKK1) Wnt-signaling pathway qPCR arrays showed that sFRP2 enhanced the Wnt3a-mediated transcriptional up-regulation of several genes regulated by Wnt3a including its antagonists, DKK1, and Naked cuticle-1 homolog (NKD1). These results support sFRP2's role as an enhancer of Wnt/beta-catenin signaling, a result with biological impact for both normal development and diverse pathologies such as tumorigenesis. Published by Elsevier Inc.