Human HGF

Bcakground

FHepatocyte Growth Factor (HGF) also known as scatter factor and hepatopoietin A, is a pleiotropic protein in the plasminogen subfamily of S1 peptidases. It is a multidomain molecule that includes an N-terminal PAN/APPLE-like domain, four Kringle domains, and a serine proteinase-like domain that has no detectable protease activity (1-5). Human HGF is secreted as an inactive 728 amino acid (aa) single chain propeptide. It is cleaved after the fourth Kringle domain by a serine protease to form bioactive disulfide-linked HGF with a 60 kDa alpha and 30 kDa beta chain. Alternate splicing generates human HGF isoforms that lack the proteinase-like domain and different numbers of the Kringle domains. Human HGF shares 91%-94% aa sequence identity with bovine, canine, feline, mouse, and rat HGF. HGF binds heparan-sulfate proteoglycans and the widely expressed receptor tyrosine kinase, HGF R/c-MET (6, 7). HGF-dependent c-MET activation is implicated in the development of many human cancers (8). HGF regulates epithelial morphogenesis by inducing cell scattering and branching tubulogenesis (9, 10). HGF induces the up-regulation of integrin alpha 2 beta 1 in epithelial cells by a selective increase in alpha 2 gene transcription (11). This integrin serves as a collagen I receptor, and its blockade disrupts epithelial cell branching tubulogenesis (11, 12). HGF can also alter epithelium morphology by the induction of nectin-1 alpha ectodomain shedding, an adhesion protein component of adherens junctions (13). In the thyroid, HGF induces the proliferation, motility, and loss of differentiation markers of thyrocytes and inhibits TSH-stimulated iodine uptake (14). HGF promotes the motility of cardiac stem cells in damaged myocardium (15).

Reference

1. Karihaloo, A. et al. (2005) Nephron Exp. Nephrol. 100:e40.

2. Hammond, D.E. et al. (2004) Curr. Top. Microbiol. Immunol. 286:21.

3. Rosario, M. and W. Birchmeier (2004) Dev. Cell 7:3.

4. Lesk, A.M. and W.D. Fordham (1996) J. Mol. Biol. 258:501.

5. Nakamura, T. et al. (1989) Nature 342:440.

6. Mizuno, K., et al. (1994) J. Biol. Chem. 269:1131.

7. Gheradi, E. et al. (2003) Proc. Natl. Acad. Sci. 100:12039.

8. Corso, S. et al. (2005) Trends Mol. Med. 11:284.

9. Maeshima, A. et al. (2000) Kid. Int. 58:1511.

10. Montesano, R. et al. (1991) Cell 67:901.

11. Chiu, S-J. et al. (2002) J. Biomed. Sci. 9:261.

12. Saelman, E.U.M. et al. (1995) J. Cell Sci. 108:3531.

13. Tanaka, Y. et al. (2002) Biochem. Biophys. Res. Commun. 299:472.

14. Mineo, R. et al. (1994) Endocrinology 145:4355.

15. Urbanek, K. et al. (2005) Circ. Res. 97:663.

Specifications

Components and Storage

Quality

SDS-PAGE

Gel filtration

Bioactivity

Documents

Human HGF