• Purity

  >95%, by SDS-PAGE with silver staining

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to inhibit the biological activity of IGF-I or IGF-II on MCF?7 human breast cancer cells. Karey, K.P.     et al. (1988) Cancer Research     48:4083. The ED    ₅₀ for this effect is 0.03-0.15 μg/mL in the presence of 14 ng/mL Recombinant Human IGF?II (Catalog # ).

• Source

  Spodoptera frugiperda,     Sf 9 (baculovirus)-derived Gly28-Lys291 Accession # P17936

• Accession #

• N-terminal Sequence    
  Analysis

  Gly28

• Predicted Molecular Mass

  29 kDa

• SDS-PAGE

  34-41 kDa, reducing conditions

Background: IGFBP-3

Insulin-like growth factor binding protein-3 (IGFBP-3) is one of six members of the insulin-like growth factor (IGF) binding protein superfamily which function to modulate the biological activity of IGF (1). Human IGFBP-3 is the major binding protein of IGF where it exists in circulation as a ternary complex with the acid-labile subunit (ALS) (2). Like other IGFBP members, human IGFBP-3 includes a cysteine-rich C-terminal domain, a highly variable central linker domain, and another  
N-terminal cystein-e-rich domain (2, 3). Human IGFBP--3 cDNA encodes a 291 amino acid (aa) precursor protein with a 27 aa signal peptide that is processed to generate the 264 aa mature protein. Mature human IGFBP-3 shares 82% aa sequence identity with both mouse and rat IGFBP-3. Post-translational glycosylation and phosphorylation of IGFBP-3 modifies the affinities of the binding protein. Proteolysis of IGFBP-3 by tissue plasminogen activator (tPA), a disintegrin and metaloproteases (ADAMs), and prostate specific antigen (PSA) contributes to IGFBP-3 degradation or a reduction in its affinity for IGF (4-6). The majority of soluble IGFBP-3 found in circulation is secreted from hepatic non-parenchymal cells. IGFBP-3 expression can be modulated by p53 as well as by various cytokines and growth factors (7, 8). In addition to its role in stabilizing and transporting circulating IGF, IGFBP-3 has been shown to potentiate EGF-EGFR-mediated cell growth through the activation of sphingosine kinase1 (SPHK1) and sphingosin-1-phosphate (S1P) (9, 10). IGFBP-3 has also been shown to modulate adipogenesis (11). Binding of IGFBP-3 to non-IGF-related ligands has been shown to regulate TGF-beta signaling, DNA damage, apoptosis, autophagy, and gene transcription (12). Interactions with non-IGF-related ligands is thought to contribute, in part, to the dichotomous stimulatory and inhibitory effects of IGFBP-3 on cell growth (2).

• References:

1. Shimasaki, S. and N. Ling (1991) Prog. Growth Factor Res. 3:243.

2. Baxter, R.C. (2013) J. Cell Commun. Signal 7:179.

3. Baxter, R.C. (2014) Nat. Rev. Cancer 14:329.

4. Mochizuki, S. et al. (2004) Biochem. Biophys. Res. Commun. 315:79.

5. Cohen, P. et al. (1994) J. Endocrinol. 142:407.

6. Bang, P. (1995) Prog. Growth Factor Res. 6:285.

7. Perks, C.M. and J.M. Holly (2008) J. Mammary Gland Biol. Neoplasia 13:455.

8. Chan, K. and E.M. Spencer (1997) Endocrine 7:95.

9. Guix, M. et al. (2008) J. Clin. Invest. 118:2609.

10. Martin, J.L. et al. (2009) J. Biol. Chem. 284:25542.

11. Chan, S.S. et al. (2009) Am. J. Physiol. Endocrinol. Metab. 296:E654.

12. Martin, J.L. and R.C. Baxter (2011) Growth Factors 29:235.

• Long Name:

  Insulin-like Growth Factor Binding Protein 3

• Entrez Gene IDs:

  3486 (Human); 16009 (Mouse)

• Alternate Names:

  acid stable subunit of the 140 K IGF complex; binding protein 29; binding protein 53; growth hormone-dependent binding protein; IBP-3; IBP3BP-53; IGF-binding protein 3; IGFBP3; IGFBP-3; insulin-like growth factor binding protein 3; insulin-like growth factor-binding protein 3