Hepatocyte growth factor
| Hepatocyte growth factor (hepapoietin A; scatter factor) |
PDB rendering based on 1bht. |
| Available structures |
| PDB |
1BHT, 1GMN, 1GMO, 1GP9, 1NK1, 1SHY, 1SI5, 2HGF, 2QJ2, 3HMS, 3HMT, 3HN4, 3MKP |
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| Identifiers |
| Symbols |
HGF; DFNB39; F-TCF; HGFB; HPTA; SF |
| External IDs |
OMIM: 142409 MGI: 96079 HomoloGene: 503 GeneCards: HGF Gene |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
3082 |
15234 |
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| Ensembl |
ENSG00000019991 |
ENSMUSG00000028864 |
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| UniProt |
P14210 |
O55027 |
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| RefSeq (mRNA) |
NM_000601.4 |
NM_010427.4 |
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| RefSeq (protein) |
NP_000592.3 |
NP_034557.3 |
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| Location (UCSC) |
Chr 7:
81.33 – 81.4 Mb |
Chr 5:
16.06 – 16.13 Mb |
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| PubMed search |
[1] |
[2] |
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Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells. It has been shown to have a major role in embryonic organ development, in adult organ regeneration and in wound healing.[1]
Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor[2]. Hepatocyte growth factor is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis, cell motility, and matrix invasion gives it a central role in angiogenesis, tumorogenesis, and tissue regeneration. It is secreted as a single inactive polypeptide and is cleaved by serine proteases into a 69-kDa alpha-chain and 34-kDa beta-chain. A disulfide bond between the alpha and beta chains produces the active, heterodimeric molecule. The protein belongs to the plasminogen subfamily of S1 peptidases but has no detectable protease activity. Alternative splicing of this gene produces multiple transcript variants encoding different isoforms.[3]
Interactions
Hepatocyte growth factor has been shown to interact with C-Met.[2][4][5]
References
- ^ Gallagher, J.T., Lyon, M. (2000). "Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens". In Iozzo, M, V.. Proteoglycans: structure, biology and molecular interactions. Marcel Dekker Inc. New York, New York. pp. 27–59.
- ^ a b Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA (February 1991). "Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product". Science 251 (4995): 802–4. PMID 1846706.
- ^ "Entrez Gene: HGF hepatocyte growth factor (hepapoietin A; scatter factor)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3082.
- ^ Comoglio, P M (1993). "Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells". EXS (SWITZERLAND) 65: 131–65. ISSN 1023-294X. PMID 8380735.
- ^ Naldini, L; Weidner K M, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan R P, Hartmann G, Zarnegar R, Michalopoulos G K (Oct. 1991). "Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor". EMBO J. (ENGLAND) 10 (10): 2867–78. ISSN 0261-4189. PMC 452997. PMID 1655405. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=452997.
Further reading
- Michalopoulos GK, Zarnegar R (1992). "Hepatocyte Growth Factor". Hepatology 15 (1): 149–54. doi:10.1002/hep.1840150125.
- Nakamura T (1992). "Structure and function of hepatocyte growth factor". Prog. Growth Factor Res. 3 (1): 67–85. doi:10.1016/0955-2235(91)90014-U. PMID 1838014.
- Ware LB, Matthay MA (2002). "Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair". Am. J. Physiol. Lung Cell Mol. Physiol. 282 (5): L924–40. doi:10.1152/ajplung.00439.2001. PMID 11943656.
- Funakoshi H, Nakamura T (2003). "Hepatocyte growth factor: from diagnosis to clinical applications". Clin. Chim. Acta 327 (1–2): 1–23. doi:10.1016/S0009-8981(02)00302-9. PMID 12482615.
- Skibinski G (2004). "The role of hepatocyte growth factor/c-met interactions in the immune system". Arch. Immunol. Ther. Exp. (Warsz.) 51 (5): 277–82. PMID 14626426.
- Kalluri R, Neilson EG (2004). "Epithelial-mesenchymal transition and its implications for fibrosis". J. Clin. Invest. 112 (12): 1776–84. doi:10.1172/JCI20530. PMC 297008. PMID 14679171. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=297008.
- Hurle RA, Davies G, Parr C et al. (2006). "Hepatocyte growth factor/scatter factor and prostate cancer: a review". Histol. Histopathol. 20 (4): 1339–49. PMID 16136515.
- Kemp LE, Mulloy B, Gherardi E (2006). "Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors". Biochem. Soc. Trans. 34 (Pt 3): 414–7. doi:10.1042/BST0340414. PMID 16709175.
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PDB gallery
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1bht: NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR
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1gmn: CRYSTAL STRUCTURES OF NK1-HEPARIN COMPLEXES REVEAL THE BASIS FOR NK1 ACTIVITY AND ENABLE ENGINEERING OF POTENT AGONISTS OF THE MET RECEPTOR
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1gmo: CRYSTAL STRUCTURES OF NK1-HEPARIN COMPLEXES REVEAL THE BASIS FOR NK1 ACTIVITY AND ENABLE ENGINEERING OF POTENT AGONISTS OF THE MET RECEPTOR
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1gp9: A NEW CRYSTAL FORM OF THE NK1 SPLICE VARIANT OF HGF/SF DEMONSTRATES EXTENSIVE HINGE MOVEMENT AND SUGGESTS THAT THE NK1 DIMER ORIGINATES BY DOMAIN SWAPPING
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1nk1: NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR (HGF/SF) AT 2.5 ANGSTROM RESOLUTION
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1shy: The Crystal Structure of HGF beta-chain in Complex with the Sema Domain of the Met Receptor.
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1si5: Protease-like domain from 2-chain hepatocyte growth factor
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2hgf: HAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE
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See also
External links
Intercellular signaling peptides and proteins / ligands |
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| Growth factors |
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| Ephrin |
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| Other |
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see also extracellular ligand disorders
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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