Hepatocyte growth factor

HGF
	Belt model according to PDB 1BHT
Properties of human protein
Identifier
External IDs	UniProt : P14210 ;

The hepatocyte growth factor ( English hepatocyte growth / scatter factor , HGF) is a paracrine growth factor that is formed by various mesenchymal cells and acts primarily on epithelial, endothelial and hematopoietic cells. HGF plays an important role in embryonic development, cell regeneration and wound healing, and in the pathogenesis of certain tumors.

function

HGF was first described in 1984 as an important growth factor for the regulation of liver growth and the regeneration of liver cells. HGF is also involved in embryonic growth and differentiation processes, including the formation of tubular structures in the kidneys and mammary glands , skeletal muscles , teeth and lungs. It is involved in the regulation of apoptosis and in the regeneration and wound healing of various tissues.

structure

HGF is expressed as a protein with a total length of 728 amino acids. Serine proteases cleave into the 69-kDa alpha chain and the 34-kDa beta chain, which remain connected via a disulfide bridge.

receptor

The receptor of HGF is c-met, a tyrosine kinase receptor that is expressed on epithelial cells and mediates the biological functions of HGF. c-met activates the downstream signaling pathways RAS , PI3K , STAT3 , beta-catenin and Notch .

Clinical significance

HGF has been shown to contribute to aggressive tumor growth, tissue infiltration, and metastasis in malignancies. The effectiveness of blocking the HGF receptor by tyrosine kinase inhibitors such as crizotinib is being investigated in clinical studies for the treatment of malignant tumors.

history

In 1984, HGF was first described as a mitogenic protein for hepatocytes from rats and subsequently also detected in human blood. A motility factor previously known as the scatter factor , which is formed by fibroblasts , was described in 1991 as being identical to HGF.

Individual evidence

^ Toshikazu Nakamura: Structure and function of hepatocyte growth factor . In: Progress in Growth Factor Research . tape 3 , no. 1 , 1991, p. 67-85 , doi : 10.1016 / 0955-2235 (91) 90014-U , PMID 1838014 .
↑ Toshikazu Nakamura, Katsuhiko Nawa, Akira Ichihara: Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats . In: Biochemical and Biophysical Research Communications . tape 122 , no. 3 , August 16, 1984, p. 1450-1459 , doi : 10.1016 / 0006-291X (84) 91253-1 .
↑ Friedhelm Bladt, Dieter Rieth maker, Stefan Isenmann, Adriano Aguzzi, Carmen Birch Meier: Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud . In: Nature . tape 376 , no. 6543 , August 31, 1995, p. 768-771 , doi : 10.1038 / 376768a0 .
↑ Takahiro Nakamura, Katsuya Sakai, Toshikazu Nakamura, Kunio Matsumoto: Hepatocyte growth factor twenty years on: Much more than a growth factor . In: Journal of Gastroenterology and Hepatology . tape 26 , January 1, 2011, p. 188–202 , doi : 10.1111 / j.1440-1746.2010.06549.x .
↑ DP Bottaro et al. a .: Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product . In: Science . tape 251 , no. 4995 , February 15, 1991, p. 802-804 , doi : 10.1126 / science.1846706 , PMID 1846706 .
↑ KM Weidner, J. Behrens, J. Vandekerckhove, W. Birchmeier: Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells . In: The Journal of Cell Biology . tape 111 , no. 5 , January 11, 1990, pp. 2097-2108 , doi : 10.1083 / jcb.111.5.2097 , PMID 2146276 .
↑ NCT00585195 A Study Of Oral PF-02341066, A c-Met / Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer ClinicalTrials.gov
↑ E. Gohda et al. a .: Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure . In: Journal of Clinical Investigation . tape 81 , no. 2 , February 1988, p. 414-419 , PMID 3276728 .
^ R. Montesano, K. Matsumoto, T. Nakamura, L. Orci: Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor . In: Cell . tape 67 , no. 5 , November 29, 1991, pp. 901-908 , doi : 10.1016 / 0092-8674 (91) 90363-4 .

[1] Toshikazu Nakamura: Structure and function of hepatocyte growth factor . In: Progress in Growth Factor Research . tape 3 , no. 1 , 1991, p. 67-85 , doi : 10.1016 / 0955-2235 (91) 90014-U , PMID 1838014 .

[2] Toshikazu Nakamura, Katsuhiko Nawa, Akira Ichihara: Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats . In: Biochemical and Biophysical Research Communications . tape 122 , no. 3 , August 16, 1984, p. 1450-1459 , doi : 10.1016 / 0006-291X (84) 91253-1 .

[3] Friedhelm Bladt, Dieter Rieth maker, Stefan Isenmann, Adriano Aguzzi, Carmen Birch Meier: Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud . In: Nature . tape 376 , no. 6543 , August 31, 1995, p. 768-771 , doi : 10.1038 / 376768a0 .

[4] Takahiro Nakamura, Katsuya Sakai, Toshikazu Nakamura, Kunio Matsumoto: Hepatocyte growth factor twenty years on: Much more than a growth factor . In: Journal of Gastroenterology and Hepatology . tape 26 , January 1, 2011, p. 188–202 , doi : 10.1111 / j.1440-1746.2010.06549.x .

[pmid1846706-5] DP Bottaro et al. a .: Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product . In: Science . tape 251 , no. 4995 , February 15, 1991, p. 802-804 , doi : 10.1126 / science.1846706 , PMID 1846706 .

[6] KM Weidner, J. Behrens, J. Vandekerckhove, W. Birchmeier: Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells . In: The Journal of Cell Biology . tape 111 , no. 5 , January 11, 1990, pp. 2097-2108 , doi : 10.1083 / jcb.111.5.2097 , PMID 2146276 .

[TrialNCT00585195-7] NCT00585195 A Study Of Oral PF-02341066, A c-Met / Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer ClinicalTrials.gov

[8] E. Gohda et al. a .: Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure . In: Journal of Clinical Investigation . tape 81 , no. 2 , February 1988, p. 414-419 , PMID 3276728 .

[9] R. Montesano, K. Matsumoto, T. Nakamura, L. Orci: Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor . In: Cell . tape 67 , no. 5 , November 29, 1991, pp. 901-908 , doi : 10.1016 / 0092-8674 (91) 90363-4 .