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

Synonyms	DFNB39; EC 3.4.21; EC 3.4.21.7; fibroblast-derived tumor cytotoxic factor; F-TCF;HGF; HGFB; HPTA
Accession #	P14210
Source	Human embryonic kidney cell, HEK293-derived human HGF protein
Source	Gln32-Ser728
Predicted Moleucular weight	53.7 kDa ( alpha chain) + 26 kDa ( beta chain)

Components and Storage

Formulation	Solution protein
	Dissolved in sterile PBS buffer.
	This solution can be diluted into other aqueous buffers. Centrifuge the vial prior to opening.
Storage and Stability	Avoid repeated freeze-thaw cycles.
	It is recommended that the protein be aliquoted for optimal storage.
	12 months from date of receipt, -20 to -70 °C as supplied.
Shipping	Shipping with dry ice.

Quality

Purity	> 95%, determined by SDS-PAGE.
Endotoxin Level	<0.010 EU per 1 ug of the protein by the LAL method.
Activity	Measured by its ability to induce IL-11 secretion by Saos-2 human osteosarcoma cells.
Activity	The EC50 for this effect is 0.05-0.2 ng/mL.

SDS-PAGE

Gel filtration

Bioactivity

Documents

Human HGF