Evolution of plasminogen-related growth factors (HGF/SF and HGF1/MSP).
HGF/SF and HGF1/MSP define a novel growth factor family whose members share the domain structure and the proteolytic process of activation of the blood proteinase precursor plasminogen. The amino acid and RNA sequences of HGF/SF and HGF1/MSP, the intron-exon organization of their genes and the predicted 3D structure of individual domains indicate that HGF/SF and HGF1/MSP evolved along with plasminogen and other members of the kringle-serine proteinase (KSP) superfamily from an ancestral gene that contained a single copy of the kringle domain, a serine proteinase domain and an activation peptide connecting the two domains. A series of intragenic duplications of the kringle domain, gene duplications, exon shuffling and deletions is responsible for the genes currently present in mammals, avians and amphibians. Plasminogen, HGF/SF and HGF1/MSP represent paradigmatic examples of the modern, multi-domain proteins typically associated with vertebrate organisms and illustrate a novel evolutionary pathway that led to the emergence of molecules with growth regulatory activity from proteolytic enzymes.
Gherardi
E
E
Imperial Cancer Research Fund Laboratory, Cambridge University Medical School, MRC Centre, UK.
Gonzalez Manzano
R
R
Cottage
A
A
Hawker
K
K
Aparicio
S
S
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D006133:Growth Substances / Q000737:chemistry*; D017228:Hepatocyte Growth Factor / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000737:chemistry*; D011498:Protein Precursors / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D017386:Sequence Homology, Amino Acid
D006133:Growth Substances; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D010958:Plasminogen