Role of CCN5 ( WNT1 inducible signaling pathway protein 2) in pancreatic islets

HighlightsCCN5 ( WNT1 inducible signaling pathway protein 2) was found to be a novel protein expressed in pancreatic β‐cells. Its normal expression is regulated directly by insulin‐like growth factor 1, in addition to W nt proteins. Initial characterization using gain‐ and loss‐of‐function approaches indicates its potential role as a novel growth factor. The mechanism of action of CCN5 seems to include AKT phosphorylation and increased cellular cyclin D1 . Domain structure of CCN ( C ysteine‐rich angiogenic inducer 61 [ Cyr61 ], C onnective tissue growth factor [ CTGF in humans], and N ephroblastoma overexpressed [ N ov; in chickens])/ WNT1 inducible signaling pathway ( WISP ) proteins: the insulin‐like growth factor‐binding protein ( IGFBP ) domain has sequence homology to IGFBP s but only confers <1% affinity for insulin‐like growth factors ( IGF s); the von W illebrand factor C ( VWC ) repeat is often seen in extracellular matrix ( ECM ) proteins; the thrombospondin type I repeat ( TSP‐1 ); and the cysteine‐rich C ‐terminal repeat ( CT ; cysteine knot or heparin‐binding domain), which is missing from CCN5 . Figure adapted from B rigstock et al.[9][Brigstock DR, 2003] and H olbourn et al. 13 , cysteine rich 61 (Cyr61), connective tissue growth factor 2 (CTGF‐2), IGFBP‐related protein 2 (IGFBP‐rP2), nephroblastoma overexpressed gene (NOV), heparin‐binding growth factor 0.8 (HBGF‐0.8), Wnt‐inducible secreted protein (Wisp), expressed in low metastatic cells (Elm‐1), heparin‐induced CCN‐like protein (HICP), card‐only protein 1 (Cop‐1).