Hepatocyte growth factor: Difference between revisions

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Michal Harel, Alexander Berchansky

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 <StructureSection load='1shy' size='350' side='right' caption='Structure of human HGF β chain (grey) complex with HGF receptor Sema and ψ domains (green) (PDB entry [[1shy]])' scene=''>
+== Function ==
+'''Hepatocyte growth factor''' (HGF) regulates cell growth, motility and morphogenesis.  HGF binds to proto-oncogene c-Met receptor and activates a tyrosine kinase signaling cascade.  HGF precursor is cleaved by serine protease to α (69 kD) and β (34 kD) chains which form a disulfide bond to produce the active heterodimer<ref>PMID:1838014</ref>.  '''HGF α chain''' contains an N-terminal hairpin and 4 kringle domains.  The kringle domain participates in protein-protein interaction and its structure is of a large loop which is stabilized by 3 Cys-Cys bonds.  '''HGF β chain''' is catalytically inactive serine protease-like.  '''HGF NK1''' - a natural splice variant is comprised of residues 28-210 containing the N-terminus and the first kringle domain of HGF<ref>PMID:9488442</ref>.  '''HGF NK2''' variant is comprised of residues 28-289 containing the N-terminus and the first 2 kringle domains of HGF. See also [[Hepatocyte growth factor receptor]].
-'''Hepatocyte growth factor''' (HGF) regulates cell growth, motility and morphogenesis.  HGF binds to proto-oncogene c-Met receptor and activates a tyrosine kinase signaling cascade.  HGF precursor is cleaved by serine protease to α and β (residues 495-728) chains which form a disulfide bond to produce the active heterodimer.  HGF NK1 variant is comprised of residues 28-210 containing the N-terminus and the first kringle domain of HGF.  HGF NK2 variant is comprised of residues 28-289 containing the N-terminus and the first 2 kringle domains of HGF.
+== Relevance ==
+High levels of HGF are associated with liver diseases<ref>PMID:7806142</ref>, lung diseases, acute cardiac infraction, vascular diseases, renal failure, neurologic diseases like Alzheimer Disease, pancreatic diseases, several types of cancer and diabetes type II<ref>PMID:19154948</ref><ref>PMID:7806142</ref>.  HGF administration can reverse liver chirrosis<ref>PMID:12482615</ref>.
+</StructureSection>
 ==3D structures of hepatocyte growth factor==
 Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+{{#tree:id=OrganizedByTopic|openlevels=0|
-===HGF N terminal===
+*HGF full length 1-728
-[[2hgf]] – hHGF N terminal – human - NMR <br />
+**[[7mo7]], [[7mo8]], [[7mo9]], [[7moa]], [[7mob]] – hHGF + hHGFR – human – Cryo EM <br />
-[[3hms]], [[3hmt]] – hHGF N terminal  <br />
-[[3hmr]] – mHGF N terminal – mouse <br />
-===HGF NK1 variant===
+*HGF N terminal 28-126
-[[1bht]], [[1nk1]], [[1gp9]], [[2qj2]], [[2qj4]] – hHGF NK1 <br />
+**[[2hgf]] – hHGF N terminal – human - NMR <br />
-[[1gmn]], [[1gmo]], [[3mkp]] – hHGF NK1 (mutant) + heparin<br />
+**[[3hms]], [[3hmt]] – hHGF N terminal  <br />
+**[[3hmr]] – mHGF N terminal – mouse <br />
-===HGF NK2 variant===
+*HGF NK1 variant 28-210
-[[3hn4]] – hHGF NK2 <br />
+**[[1bht]], [[1nk1]], [[1gp9]], [[2qj2]], [[2qj4]] – hHGF NK1 <br />
-[[3sp8]] – hHGF NK2 (mutant) + heparin<br />
+**[[5cs1]], [[5cs5]], [[5cs9]], [[5coe]] – hHGF NK1 (mutant) <br />
-[[4iua]] – mHGF NK2 (mutant) <br />
+**[[1gmn]], [[1gmo]], [[3mkp]] – hHGF NK1 (mutant) + heparin<br />
+**[[5ct1]], [[5ct2]], [[5ct3]], [[5cs3]], [[5csq]], [[5cp9]] – hHGF NK1 (mutant) + inhibitor<br />
+**[[4d3c]] – hHGF NK1 (mutant) + antibody<br />
-===HGF β chain===
+*HGF NK2 variant 28-289
-[[1si5]] – hHGF β chain (mutant) <br />
+**[[3hn4]] – hHGF NK2 <br />
-[[1shy]] – hHGF β chain (mutant) + HGF receptor Sema and ψ domains<br />
+**[[3sp8]] – hHGF NK2 (mutant) + heparin<br />
+**[[4iua]] – mHGF NK2 (mutant) <br />
-===HGF α+β chain===
+* HGF α chain (69 kD) 495-728
+**[[1si5]] – hHGF  α chain (mutant) <br />
+**[[1shy]] – hHGF α  chain (mutant) + HGF receptor Sema and ψ domains<br />
+*HGF β chain  25-567
+**[[4o3t]], [[4o3u]] – hHGF β  chain (mutant) + HGF receptor Sema and ψ domains + zymogen activator peptide<br />
+*HGF α+β chain
+**[[4k3j]] – hHGF α (mutant) + β + antibody <br />
+**[[6lz9]] – hHGF α (mutant) + K4 domain 388-494 + antibody <br />
+}}
+== References ==
+<references/>
-[[4k3j]] – hHGF α (mutant) + β + antibody <br />
 [[Category:Topic Page]]