title: Nephroblastoma overexpressed gene (NOV) codes for a growth factor that induces protein tyrosine phosphorylation.
abstract: NOV (nephroblastoma overexpressed gene) is a member of the CCN (connective tissue growth factor [CTGF], Cyr61/Cef10, NOV) family of proteins. These proteins are cysteine-rich and are noted for having growth-regulatory functions. We have isolated the rat NOV gene, and the DNA sequence shares 90% identity with the mouse and 80% identity with the human sequences. The rat NOV gene was expressed in all rat tissues examined, including brain, lung, heart, 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 other tissues. Examination of NOV expression in various human cell lines revealed that NOV was expressed in U87, 293, T98G, SK-N-MC and Hs683 but not in HepG2, HL60, THP1 and Jurkat. The human NOV gene was transfected into 293 cells and the expressed protein purified. When 3T3 fibroblasts were treated with this recombinant NOV protein, a dose-dependent increase in proliferation was observed. Analysis of tyrosine-phosphorylated proteins revealed that when 3T3 cells were treated with NOV, a 221 kDa protein was phosphorylated. These data suggest that NOV can act as a growth factor for some cells and binds to a specific receptor that leads to the phosphorylation of a 221 kDa protein.
authors.affiliation: Neurocrine Biosciences Inc., San Diego, CA 92121, USA. cliu@neurocrine.com
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: X J
authors.initials: XJ
authors.lastname: Liu
authors.forename: P D
authors.initials: PD
authors.lastname: Crowe
authors.forename: G S
authors.initials: GS
authors.lastname: Kelner
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.forename: G
authors.initials: G
authors.lastname: Barry
authors.forename: F
authors.initials: F
authors.lastname: Manu
authors.forename: N
authors.initials: N
authors.lastname: Ling
authors.forename: E B
authors.initials: EB
authors.lastname: De Souza
authors.forename: R A
authors.initials: RA
authors.lastname: Maki
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D003001:Cloning, Molecular; D055513:Connective Tissue Growth Factor; D018076:DNA, Complementary; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007680:Kidney Neoplasms / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D055514:Nephroblastoma Overexpressed Protein; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C526316:CCN2 protein, rat; C526319:CCN3 protein, human; C526320:Ccn3 protein, mouse; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D014443:Tyrosine; D003907:Dexamethasone