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Binding properties and distribution of insulin-like growth factor binding protein-related protein 3 (IGFBP-rP3/NovH), an additional member of the IGFBP Superfamily.

The protein product of the novH oncogene, a member of the CCN family, is structurally related to the insulin-like growth factor (IGF) binding proteins (IGFBPs). We have characterized aspects of structure, function, and distribution of this protein, which, as IGFBP-related protein 3 (IGFBP-rP3), is a proposed member of the IGFBP Superfamily. Affinity cross-linking experiments performed with baculovirus synthesized recombinant human IGFBP-rP3 established that rhIGFBP-rP3 binds IGF-I, IGF-II, and insulin with low affinity. Specificity of binding was shown by competitive cross-linking experiments; binding to IGF-I and -II was also demonstrated by nondenaturing Western ligand blots. Northern blot analysis indicated the presence of IGFBP-rP3 messenger RNA (mRNA) in a broad range of human tissues. Western immunoblotting studies, using a polyclonal rabbit anti-rhIGFBP-rP3 antibody, demonstrated that IGFBP-rP3 protein is synthesized in vitro by several breast and prostate cancer cell lines: Hs578T, PC3, P69, and LNCaP cells. Western immunoblotting studies of human biological fluids identified that IGFBP-rP3 was present in normal serum, pregnancy serum, serum from patients with growth hormone receptor deficiency, cerebrospinal fluid, amniotic fluid, peritoneal fluid, and follicular fluid, while IGFBP-rP3 fragments were identified in cerebrospinal fluid, amniotic fluid, and prepubertal and pubertal urine samples. Our studies demonstrate that IGFBP-rP3 exhibits IGF binding, albeit at low affinity, and IGFBP-rP3 thus merits inclusion in the IGFBP Superfamily. The low affinity IGF binding suggests that IGFBP-rP3 may act primarily independently of the IGFs. The synthesis of IGFBP-rP3 by several malignant cell lines and its presence in human biological fluids suggest that this protein possesses other interesting roles, potentially in cell growth regulation.

Pubmed ID: 10084601


  • Burren CP
  • Wilson EM
  • Hwa V
  • Oh Y
  • Rosenfeld RG


The Journal of clinical endocrinology and metabolism

Publication Data

March 13, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA58110
  • Agency: NIDDK NIH HHS, Id: DK51513

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antibodies
  • Cell Line
  • Connective Tissue Growth Factor
  • Epitopes
  • Female
  • Growth Substances
  • Humans
  • Immediate-Early Proteins
  • Insulin-Like Growth Factor Binding Protein 3
  • Intercellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Nephroblastoma Overexpressed Protein
  • Oligopeptides
  • Peptides
  • Pregnancy
  • RNA, Messenger
  • Rabbits
  • Recombinant Proteins
  • Sequence Tagged Sites
  • Tissue Distribution