Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a family of polypeptides named after HDGF, which was identified by its mitogenic activity towards fibroblasts. In the present study, we describe a hitherto unknown HRP, termed HRP-4. The cDNA of bovine HRP-4 (bHRP-4) predicts a polypeptide of 235 amino acids. Northern- and Western-blot analyses of various bovine tissues demonstrated that HRP-4 is only expressed in the testis. Recombinantly produced bHRP-4 and murine HDGF (mHDGF) histidine-tagged polypeptides display growth-factor activity for cultured primary human fibroblasts at an optimum concentration of 1ng/ml in serum-free medium. The growth-factor activity declines with increasing concentrations to reach background levels at 1μg/ml. The expression of the fusion proteins, bHRP-4–green fluorescent protein and mHDGF–green fluorescent protein, in HEK-293 cells demonstrates nuclear localization of the proteins. bHRP-4 and mHDGF bind to the glycosaminoglycans heparin and heparan sulphate, but not to chondroitin sulphate. Affinity constants determined for these interactions are between 6 and 42nM. Comparison of the bHRP-4 amino acid sequence with HRP-1–3 and p52/75/lens epithelium-derived growth factor (LEDGF) shows that these proteins share a conserved N-terminal part of 91 amino acids but have C-termini of different lengths and charge. This demonstrates the modular structure of these proteins and allows its classification into three groups based on charge, size and sequence comparison. HRP-4, HRP-1 and HDGF are small acidic proteins, HRP-3 is a small basic protein, and HRP-2 and p52/75/LEDGF are larger basic proteins.
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September 2002
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Research Article|
September 01 2002
The family of hepatoma-derived growth factor proteins: characterization of a new member HRP-4 and classification of its subfamilies
Frank DIETZ;
Frank DIETZ
1
∗Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms Universität, Nussallee 11, 53115 Bonn, Germany,
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Sebastian FRANKEN;
Sebastian FRANKEN
2
∗Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms Universität, Nussallee 11, 53115 Bonn, Germany,
2To whom correspondence should be addressed (e-mail franken@institut.physiochem.uni-bonn.de).
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Kenya YOSHIDA;
Kenya YOSHIDA
†Department of Molecular Medicine, Osaka University Medical School, Yamada-oka 2-2, Suita 565-0871, Osaka, Japan
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Hideji NAKAMURA;
Hideji NAKAMURA
†Department of Molecular Medicine, Osaka University Medical School, Yamada-oka 2-2, Suita 565-0871, Osaka, Japan
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Joachim KAPPLER;
Joachim KAPPLER
∗Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms Universität, Nussallee 11, 53115 Bonn, Germany,
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Volkmar GIESELMANN
Volkmar GIESELMANN
∗Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms Universität, Nussallee 11, 53115 Bonn, Germany,
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Publisher: Portland Press Ltd
Received:
December 10 2001
Revision Received:
April 18 2002
Accepted:
May 13 2002
Accepted Manuscript online:
May 13 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (2): 491–500.
Article history
Received:
December 10 2001
Revision Received:
April 18 2002
Accepted:
May 13 2002
Accepted Manuscript online:
May 13 2002
Citation
Frank DIETZ, Sebastian FRANKEN, Kenya YOSHIDA, Hideji NAKAMURA, Joachim KAPPLER, Volkmar GIESELMANN; The family of hepatoma-derived growth factor proteins: characterization of a new member HRP-4 and classification of its subfamilies. Biochem J 1 September 2002; 366 (2): 491–500. doi: https://doi.org/10.1042/bj20011811
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