Nephroblastoma overexpressed gene (NOV) codes for a growth factor that induces protein tyrosine phosphorylation

NOV (nephroblastoma overexpressed gene) is a member of the CCN (connective tissue growth factor [CTGF], Cyr61/Cef10, NOV) family of proteins. These pr oteins are cysteine-rich and are noted for having growth-regulatory functio ns. We have isolated the rat NOV gene, and the DNA sequence shares 90% iden tity with the mouse and 80% identity with the human sequences. The rat NOV gene was expressed in all rat tissues examined, including brain, lung, hear t, kidney, liver, spleen, thymus and skeletal muscle. Higher levels of rat NOV mRNA were seen in the brain, lung and skeletal muscle compared to the o ther tissues. Examination of NOV expression in various human cell lines rev ealed that NOV was expressed in U87, 293, T98G, SK-N-MC and Hs683 but not i n HepG2, HL60, THP1 and Jurkat. The human NOV gene was transfected into 293 cells and the expressed protein purified. When 3T3 fibroblasts were treate d with this recombinant NOV protein, a dose-dependent increase in prolifera tion was observed. Analysis of tyrosine-phosphorylated proteins revealed th at when 3T3 cells were treated with NOV, a 221 kDa protein was phosphorylat ed. These data suggest that NOV can act as a growth factor for some cells a nd binds to a specific receptor that leads to the phosphorylation of a 221 kDa protein. (C) 1999 Elsevier Science B.V. All rights reserved.